Co-reporter:Shijia Tang, Ke Hu, Jianfei Sun, Yang Li, Zhaobin Guo, Mei Liu, Qi Liu, Feimin Zhang, and Ning Gu
ACS Applied Materials & Interfaces March 29, 2017 Volume 9(Issue 12) pp:10446-10446
Publication Date(Web):March 1, 2017
DOI:10.1021/acsami.6b15918
In recent years, multicellular spheroid (MCS) culture has been extensively studied both in fundamental research and application fields since it inherits much more characteristics from in vivo solid tumor than conventional two-dimensional (2D) cell culture. However, anticell adhesive MCS culture systems such as hanging drop allow certain cell lines only to form loose, irregular aggregates rather than MCS with physiological barriers and pathophysiological gradients, which failed to mimic in vivo solid tumor in these aspects. To address this issue, we improved our previously established anisotropic magnetic hydrogel platform, enabling it to generate multicellular spheroids with higher efficiency. The qualities of multicellular tumor spheroids (MCTSs) obtained on our platform and from classic 3D culture systems were compared in terms of morphology, biological molecule expression profiles, and drug resistance. In this novel platform, mature MCTSs with necrotic cores could be observed in 1 week. And results of molecular biological assays with real time-PCR and western-blot confirmed that MCTSs obtained from our platform performed higher cell pluripotency than those obtained from the hanging drop system. Moreover, a lower cell apoptosis ratio and better viability of cancer cells were observed on our platform both under culturing and drug treatment. In conclusion, higher quality of MCTSs obtained from this anisotropic magnetic hydrogel than classic hanging drop system validate its potential to be an in vitro platform of inducing tumor MCTS formation and drug efficacy evaluation.Keywords: 3D cell culture; anisotropic magnetic hydrogel; cell−matrix interaction; microenvironment; multicellular tumor spheroids;
Co-reporter:Meng Wang;Min Cao
The Journal of Physical Chemistry C January 29, 2009 Volume 113(Issue 4) pp:1217-1221
Publication Date(Web):2017-2-22
DOI:10.1021/jp808000x
On the basis of a quasi-static theory, the sensitivity of surface plasmon resonance to the refractive index of the surrounding medium is investigated for gold nanoboxes with fixed inner edge length. It is found that the refractive index sensitivity increases near-exponentially as the wall thickness is decreased. However, decreasing wall thickness results in an excessive broadening of the resonant line width, which make the detection of the wavelength changes experimentally difficult. A figure of merit (FOM) is therefore calculated. According to the FOM, there exists an optimum wall thickness for gold nanoboxes to have the best performance. Both the refractive index sensitivity and the FOM of the gold nanoboxes are relatively high in comparison with that of other gold nanostructures, making them potential candidates for chemical and biological sensing applications.
Co-reporter:Jilai Tian, Caiyun Yan, Kunliang Liu, Juan Tao, ... Ning Gu
Journal of Pharmaceutical Sciences 2017 Volume 106, Issue 8(Volume 106, Issue 8) pp:
Publication Date(Web):1 August 2017
DOI:10.1016/j.xphs.2017.04.023
Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid therapy in critical patients in clinic integrated system. Herein, we synthesized paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)-lysine-oleic acid2 (PTX-MNPs-PLO), which is expected to act as a magnetic resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs were synthesized by thermal decomposition. Dialysis method was applied to prepare PTX-MNPs-PLO with 3 different PEG molecular weights (1000, 2000, and 4000 Da), which were subsequently freeze-dried into powders. PTX-MNPs-PLO was characterized by transmission electron microscope, scanning electron microscope, thermogravimetric analysis, vibrating sample magnetometer, and MRI. What is more is that pharmacokinetics and distribution in vivo were processed, the results of which exhibited that PTX-MNPs-PLO2000 had the longer circulation lifetime compared with Taxol, PTX-MNPs-PLO1000, and PTX-MNPs-PLO4000. Results of magnetic targeting in kidneys suggested that deep buried or ultrasmall magnet is likely to be more preferable. PTX-MNPs-PLO2000 holds great promise in the application of magnetic accumulation, target drug delivery, and thermal therapy.
Co-reporter:Yuwei Zhou, Ke Hu, Zhaobin Guo, Kun Fang, Xing Wang, Fang Yang, Ning Gu
Materials Science and Engineering: C 2017 Volume 78(Volume 78) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.msec.2017.04.100
•Chlorhexidine acetate (CA) was applied as both antimicrobial drug and surfactant for microcapsule preparation.•With CA and silver nanoparticle, composite microcapsules promise a rapid and sustained antibacterial effect.•Composite microcapsules can be modified on the surface of polymer film, promising applications on surgical dressing, etc.In this study, composite antibacterial microcapsules combining of two antibacterial agents: chlorhexidine acetate and silver nanoparticle were prepared. The chlorhexidine acetate was encapsulated inside of the microcapsules and nano-sized silver particles were modified on the surface of microcapsules by electrostatic adsorption methods. Results show that this method decreases the silver usage dramatically, and promises a sustained antibacterial effect > 30 days. These microcapsules can also be modified on the surface of polymer films easily, which demonstrated the potential in functionalizing the implanted materials with antibacterial property.Download high-res image (73KB)Download full-size image
Co-reporter:Zuoheng Zhang, Xubo Lin, Ning Gu
Colloids and Surfaces B: Biointerfaces 2017 Volume 160(Volume 160) pp:
Publication Date(Web):1 December 2017
DOI:10.1016/j.colsurfb.2017.09.013
•Higher temperature could accelerate the translocation of NPs.•Steric hindrance effects of PEG would inhibit NPs’ translocation.•PEG could rearrange themselves to minimize the contacts with lipid tails.•Flip-flops were affected by PEGylated density and NPs’ translocation direction.Plasma membrane internalization of nanoparticles (NPs) is important for their biomedical applications such as drug-delivery carriers. On one hand, in order to improve their half-life in circulation, PEGylation has been widely used. However, it may hinder the NPs’ membrane internalization ability. On the other hand, higher temperature could enhance the membrane permeability and may affect the NPs’ ability to enter into or exit from cells. To make full use of their advantages, we systematically investigated the effects of temperature and PEG density on the translocation of PEGylated nanoparticles across the plasma asymmetric membrane of eukaryotic cells, using near-atom level coarse-grained molecular dynamics simulations. Our results showed that higher temperature could accelerate the translocation of NPs across membranes by making lipids more disorder and faster diffusion. On the contrary, steric hindrance effects of PEG would inhibit NPs’ translocation process and promote lipids flip-flops. The PEG chains could rearrange themselves to minimize the contacts between PEG and lipid tails during the translocation, which was similar to ‘snorkeling effect’. Moreover, lipid flip-flops were affected by PEGylated density as well as NPs’ translocation direction. Higher PEG grafting density could promote lipid flip-flops, but inhibit lipid extraction from bilayers. The consequence of lipid flip-flop and extraction was that the membranes got more symmetric.We investigated effects of temperature and PEG density on the translocation aross biomembrane and properties of nanoparticles and lipid bilayers.Download high-res image (298KB)Download full-size image
Co-reporter:Wei Zhang, Jinlai Dong, Yang Wu, Peng Cao, Lina Song, Ming Ma, Ning Gu, Yu Zhang
Colloids and Surfaces B: Biointerfaces 2017 Volume 154(Volume 154) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.colsurfb.2017.02.034
•The influence of exposed crystal planes on the catalytic activities of Co3O4 NPs.•EGFR sdAbs were conjugated with Co3O4 NPs using a simple blending method.•Effective detection of EGFR of NSCLC tissues was realized.In this study, Co3O4 nanopolyhedrons, nanocubes, nanoplates and nanorods were synthesized and characterized. Furthermore, the peroxidase- and catalase-like activities of these Co3O4 nanoparticles (NPs) were studied and influence of the exposed crystal planes was explored. According to their morphology and peroxidase-like activity, dimercaptosuccinic acid (DMSA) modified Co3O4 nanopolyhedrons synthesized via coprecipitation method (Co3O4 NHs) were selected as a proper candidate for the immunohistochemical (IHC) detection of epidermal growth factor receptor (EGFR) expression in non-small cell lung cancer (NSCLC) tissues. Bivalent cobalt ions were coupled to the carboxyls on the surface of the obtained Co3O4 NHs so as to chelate the hexahistidine residues (His-Tags) at the C-terminal of EGFR single-domain antibodies (EGFR sdAbs). Finally, the as-obtained EGFR sdAbs-binding Co3O4 NHs (Co3O4 nanoprobes) were successfully applied to the detection of EGFR expression in NSCLC tissues.Download high-res image (152KB)Download full-size image
Co-reporter:Yue Zhang, Zhichao Lou, Xubo Lin, Qiwei Wang, Meng Cao, Ning Gu
Colloids and Surfaces B: Biointerfaces 2017 Volume 157(Volume 157) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.colsurfb.2017.05.054
•Different purification processes were evaluated by AFM and molecular dynamics simulations.•AFM results illustrate the importance of desalination process to remove the excessive imidazole.•The purity of the obtained protein was up to ∼90% after the purification processes.•MIM monomers and dimers were observed and confirmed by AFM and molecular dynamics simulations.MIM (missing in metastasis) is a member of I-BAR (inverse BAR) domain protein family, which functions as a putative metastasis suppressor. However, methods of gaining high purity MIM-I-BAR protein are barely reported. Here, by optimizing the purification process including changing the conditions of cell lysate and protein elution, we successfully purified MIM protein. The purity of the obtained protein was up to ∼90%. High-resolution atomic force microscope (AFM) provides more visual images, ensuring that we can observe the microenvironment around the target protein, as well as the conformations of the purification products following each purification process. MIM protein with two different sizes were observed on mica surface with AFM. Combining with molecular dynamics simulations, these molecules were revealed as MIM monomer and dimer. Furthermore, our study attaches importance to the usage of imidazole with suitable concentrations during the affinity chromatography process, as well as the removal of excessive imidazole after the affinity chromatography process. All these results indicate that the method described here was successful in purifying MIM protein and maintaining their natural properties, and is supposed to be used to purify other proteins with low solubility.Download high-res image (138KB)Download full-size image
Co-reporter:Yang Li, Ke Hu, Bo Chen, Yijun Liang, Fengguo Fan, Jianfei Sun, Yu Zhang, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2017 Volume 520(Volume 520) pp:
Publication Date(Web):5 May 2017
DOI:10.1016/j.colsurfa.2017.01.073
•Fe3O4 nanoparticle clusters with enhanced magnetic properties were prepared successfully by ACMF-assisted co-precipitation.•The magnetic effect as well as heat effect of ACMF on Fe3O4 nanoparticles plays a key role in the enhancement of magnetic properties during the whole synthesis process.•This strategy might hold promise in preparation of high performance magnetic nanomaterials in the future.Field-assisted synthesis has been one of the common strategies of nanoparticles preparation with enhanced properties. However, most researches focused on exploring the effects of monofunctional static field on the structure and properties of synthetic nanomaterials, few researchers have applied fields with period variation as assistance. Combining medium alternating current magnetic field with most widely used method traditional chemical co-precipitation held potential in preparation high quality Fe3O4 nanoparticle. In this study, Fe3O4 nanoparticle clusters were prepared in alternating-current magnetic field (ACMF) by co-precipitation principle, structural and magnetic properties were also characterized. Results demonstrated that Fe3O4 nanoparticle clusters prepared by co-precipitation heated in ACMF indicated a better heat production under ACMF, comparing with Fe3O4 nanoparticle clusters with similar size and distribution prepared by classic co-precipitation. It might be due to the magnetic effects induced by ACMF that Fe3O4 nanoparticles tend to grow along the magnetization direction. This technology might hold promise in preparation high performance magnetic nanomaterial in the future.Download high-res image (156KB)Download full-size image
Co-reporter:Yi-Jun Liang, Fengguo Fan, Ming Ma, Jianfei Sun, Jun Chen, Yu Zhang, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2017 Volume 530(Volume 530) pp:
Publication Date(Web):5 October 2017
DOI:10.1016/j.colsurfa.2017.06.059
•High performance Fe3O4 NPs with different sizes were ultra-fast prepared by microwave assisted thermal decomposition approach.•The size-dependent electromagnetic properties of these Fe3O4 NPs were studied systematically.•The micromagnetic simulation (OOMMF) was used to insightfully understand the size effect associated with energy variation in electromagnetic filed.A great deal of effort has demonstrated magnetite nanoparticles (Fe3O4 NPs) are important subject applied in tumor hyperthermia due to their excellent magneto-thermal effect. Our previous study had ultrafast prepared 6nm Fe3O4 NPs via microwave approach and found that these small size NPs are responsible for microwave energy conversion to accelerate NPs formation. Hence, we suppose that investigating the size-dependent behavior of Fe3O4 NPs should be beneficial for developing their electromagnetic energy conversion application for hyperthermia. In this study, Fe3O4 NPs with four sizes (i.e. 4nm, 20nm, 50nm and 200nm) were prepared by a rapid microwave synthetic strategy. The specific absorption rate (SAR) value and reflection loss (RL) value of samples were investigated by measuring the time-dependent temperature curves in alternating magnetic field (AMF, 390 and 780kHz, 12A) and via vector network analyzer (VNA) range from 2 to 18GHz, respectively. Results indicated that using magnetic induction hyperthermia frequency Fe3O4 NPs with single domain size of 20nm possess maximum, whereas the RL value increases with the size at microwave frequency. More importantly, the frequency of maximum RL value was matched with the clinical microwave hyperthermia. We subsequently introduce the micromagnetic (OOMMF) simulation to help understanding the issue due to the fundamental importance of size effect for magnetic NPs in energy conversion. Simulation results suggested that coupling interaction and magnetic dipole-dipole interaction between magnetic NPs and electromagnetic field would be seen as synergistic effect to impact absorption behavior, and we believe that this work can provide a valuable reference for size selection of magnetic nanoparticles in clinical application of hyperthermia.To insightfully understand the size-dependent electromagnetic properties of magnetic NPs will be of great importance to explore their microwave applications.Download high-res image (186KB)Download full-size image
Co-reporter:Lingying Zhu;Dawei Guo;Lili Sun;Zhihai Huang;Xiuyan Zhang;Wenjuan Ma;Jie Wu;Lun Xiao;Yun Zhao
Nanoscale (2009-Present) 2017 vol. 9(Issue 17) pp:5489-5498
Publication Date(Web):2017/05/04
DOI:10.1039/C6NR08188F
Silver nanoparticles (AgNPs) are the most commonly used engineered nanomaterials in commercialized products because of their antimicrobial activity. Previously, we have shown that polyvinylpyrrolidone (PVP)-coated AgNPs have an anti-leukemia effect against human myeloid leukemia cells; however, whether AgNPs are able to trigger autophagy in normal hematopoietic cells and the role of autophagy in AgNP-induced cytotoxicity remain unclear. In the current study, we observed that AgNPs were taken up by murine pro-B cells (Ba/F3), and then promoted accumulation of autophagosomes, which resulted from the induction of autophagy rather than the blockade of autophagic flux. AgNPs induced cytotoxicity in a dose-dependent manner accompanied by apoptosis and DNA damage through the production of reactive oxygen species (ROS) and the release of silver ions. The ROS-mediated mTOR signaling pathway was responsible for the induction of autophagy. More importantly, the inhibition of autophagy with the addition of 3-methyladenine (3-MA) or silencing of Atg5 significantly attenuated the cytotoxicity of AgNPs in Ba/F3. These findings suggest that autophagy is involved in the cytotoxicity of PVP-coated AgNPs in normal hematopoietic cells, and the inhibition of autophagy is a novel and potent strategy to protect normal hematopoietic cells upon treatment with AgNPs.
Co-reporter:Jin-Long Chen;Li Li;Shuo Wang;Xiao-Yan Sun;Lu Xiao;Jia-Shu Ren;Bin Di
Journal of Materials Chemistry B 2017 vol. 5(Issue 27) pp:5336-5344
Publication Date(Web):2017/07/12
DOI:10.1039/C7TB00864C
Daily monitoring of blood glucose is of great importance for the treatment of diabetes mellitus. Herein, we present an ensemble glucometer with a sandwich structure formed by the spontaneous entrapment of glucose oxidase (GOD) onto manganese dioxide nanosheets (MnO2 NSs) via the hydrophobic effect and hydrogen bond interaction. Within the hybrid glucometer, the ultrathin MnO2 NSs act as an enzyme nanosupport and target-activated signal transducer. Trimodal self-indication by fluorescence (FL) and UV-absorbance (UV) and magnetic resonance signal (MRS) activation with glucose-specificity provides multiple response signals to glucose. Taking account of its operational simplicity and convenience, even being observable by the naked eye, a detection limit as low as 0.1 µM was obtained by using the ensemble glucometer in a colorimetric assay, whilst the precision for 11 replicated detections of 10 µM glucose was 3.5% (relative standard deviation, RSD). Notably, the value of the Michaelis–Menton constant of GOD involved the presented glucometer is estimated to be 0.051 mM, showing an exceptional enhanced enzymatic activity of free GOD measured by far. The designed glucometer, with its high sensitivity and simplicity highlighted, was capable of routine blood glucose monitoring for type-I diabetes mellitus in rats. Furthermore, the fully integrated platform can be readily generalized in principle for a number of biomarkers for point of care diagnostics in the future.
Co-reporter:Qiwei Wang;Bo Chen;Fang Ma;Shikang Lin;Meng Cao;Yan Li
Nano Research 2017 Volume 10( Issue 6) pp:2192-2192
Publication Date(Web):12 April 2017
DOI:10.1007/s12274-017-1566-7
Co-reporter:Yang Liu 刘洋;Mingxi Li 李明熹;Fang Yang 杨芳 顾宁
Science China Materials 2017 Volume 60( Issue 6) pp:471-486
Publication Date(Web):01 June 2017
DOI:10.1007/s40843-017-9049-0
There has been unprecedented progress in the development of biomedical nanotechnology and nanomaterials over the past few decades, and nanoparticle-based drug delivery systems (DDSs) have great potential for clinical applications. Among these, magnetic drug delivery systems (MDDSs) based on magnetic nanoparticles (MNPs) are attracting increasing attention owing to their favorable biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of superparamagnetic maghemite (γ-Fe2O3) or magnetite (Fe3O4) nanoparticles ranging in size from 10 to 100 nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbubbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically modulating dosing regimens, which are the current challenges for clinical applications.随着过去几十年来生物医学纳米技术和纳米材料领域的持续发展, 基于纳米颗粒的药物输送系统逐渐开始有望应用于临床研究. 其 中, 由于具有良好的生物相容性和优异的多功能负载能力, 基于磁性纳米粒子的磁性药物传递系统受到越来越多的关注. 本综述首先总结 了磁性药物传递系统的基本物理化学性质, 以阐明磁性药物传递系统需要保持适当的性能以满足特定的临床需要; 其次, 讨论了在设计未 来临床应用的磁性药物传递系统时的表面修饰和功能化问题; 最后, 重点综述了磁性纳米颗粒、磁性组装体以及磁性微泡、磁性脂质体和 生物膜修饰的磁性载体系统的设计和制备最新进展. 最后, 本综述对目前研究的磁性载体系统的设计、制备和安全性进行了总结, 并对未 来进一步解决磁性药物传递系统的临床应用瓶颈和前景进行了展望.
Co-reporter:Gaoxin Zhou;Lushen Li;Jing Xing;Jin Cai
Journal of Sol-Gel Science and Technology 2017 Volume 82( Issue 2) pp:490-499
Publication Date(Web):2017 May
DOI:10.1007/s10971-017-4330-2
Mesoporous silica nanoparticle was expected to provide a versatile drug delivery platform with modification flexibility. To improve its hemocompatibility and realize controlled and/or targeting drug release, modification of bare mesoporous silica nanoparticles is essential. Herein, a novel method of coating mesoporous silica nanoparticles with lipid bilayers was developed. First, a homemade organosiloxane precursor was used for hydrophobic modification of mesoporous silica nanoparticles, then phospholipids (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]) were coated by a filming-rehydration method based on hydrophobic interaction. The nanoparticle samples were characterized by transmission electron microscope, dynamic light scattering, nitrogen sorption, Fourier transform infrared, and thermal gravimetric analysis. Furthermore, the novel lipid bilayer coated mesoporous silica nanoparticles were compared with bare mesoporous silica nanoparticles in terms of suspension stability, drug release, hemolysis, and nonspecific protein absorption. Our data proved that lipid bilayer coated mesoporous silica nanoparticles had better hemobiocompatibility and controlled drug release properties than that of bare mesoporous silica nanoparticles.Open image in new window
Co-reporter:Yang Liu, Fang Yang, Chuxiao Yuan, Mingxi Li, Tuantuan Wang, Bo Chen, Juan Jin, Peng Zhao, Jiayi Tong, Shouhua Luo, and Ning Gu
ACS Nano 2017 Volume 11(Issue 2) pp:
Publication Date(Web):January 3, 2017
DOI:10.1021/acsnano.6b06815
Nanosized drug delivery systems have offered promising approaches for cancer theranostics. However, few are effective to simultaneously maximize tumor-specific uptake, imaging, and therapy in a single nanoplatform. Here, we report a simple yet stimuli-responsive anethole dithiolethione (ADT)-loaded magnetic nanoliposome (AML) delivery system, which consists of ADT, hydrogen sulfide (H2S) pro-drug, doped in the lipid bilayer, and superparamagnetic nanoparticles encapsulated inside. HepG2 cells could be effectively bombed after 6 h co-incubation with AMLs. For in vivo applications, after preferentially targeting the tumor tissue when spatiotemporally navigated by an external magnetic field, the nanoscaled AMLs can intratumorally convert to microsized H2S bubbles. This dynamic process can be monitored by magnetic resonance and ultrasound dual modal imaging. Importantly, the intratumoral generated H2S bubbles imaged by real-time ultrasound imaging first can bomb to ablate the tumor tissue when exposed to higher acoustic intensity; then as gasotransmitters, intratumoral generated high-concentration H2S molecules can diffuse into the inner tumor regions to further have a synergetic antitumor effect. After 7-day follow-up observation, AMLs with magnetic field treatments have indicated extremely significantly higher inhibitions of tumor growth. Therefore, such elaborately designed intratumoral conversion of nanostructures to microstructures has exhibited an improved anticancer efficacy, which may be promising for multimodal image-guided accurate cancer therapy.Keywords: hydrogen sulfide; in situ microbubbles; magnetic nanoliposomes; multimodal imaging; ultrasound theranostics;
Co-reporter:Yan Yang 杨燕;Qiwei Wang 王琪炜;Lina Song 宋丽娜;Xuan Liu 刘璇
Science China Materials 2017 Volume 60( Issue 9) pp:892-902
Publication Date(Web):05 September 2017
DOI:10.1007/s40843-017-9088-9
With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into cells has become a primary issue for effectively regulating the subsequent safety and performance of nanomaterials in vivo. Although the influence of nanomaterials on endocytosis has been extensively studied, reports on the influence of stem cells are rare. Moreover, the effect of nanomaterials on stem cells is also dependent upon the action mode. Unfortunately, the interaction between stem cells and assembled nanoparticles is often neglected. In this paper, we explore for the first time the uptake of γ-Fe2O3 nanoparticles by adipose-derived stem cells with different passage numbers. The results demonstrate that cellular viability decreases and cell senescence level increases with the extension of the passage number. We found the surface appearance of cellular membranes to become increasingly rough and uneven with increasing passage numbers. The iron content in the dissociative nanoparticles was also significantly reduced with increases in the passage number. However, we observed multiple-passaged stem cells cultured on assembled nanoparticles to have similarly low iron content levels. The mechanism may lie in the magnetic effect of γ-Fe2O3 nanoparticles resulting from the field-directed assembly. The results of this work will facilitate the understanding and translation of nanomaterials in the clinical application of stem cells.随着纳米材料在组织工程和再生医学中越来越多的应用, 干细胞和纳米材料之间的相互作用成为关键环节, 而纳米颗粒进入细胞是关系到纳米材料安全性和干细胞命运调控的首要问题. 干细胞传代是其应用中必不可少的过程, 但关于传代代数对干细胞摄取纳米颗粒的影响的研究还较少. 此外, 干细胞和纳米材料的相互作用还与纳米颗粒的存在方式有关. 本文在玻璃片上组装了条带状的γ-Fe2O3纳米颗粒组装结构, 并在该表面上培养SD大鼠脂肪间充质干细胞, 然后研究了不同代数的干细胞对组装和游离的纳米颗粒的吞噬情况. 结果发现, 随着细胞代数增加,细胞活力降低, 细胞衰老水平增加, 并且细胞膜的表面呈现出粗糙和不均匀的形貌. 当与游离的γ-Fe2O3纳米颗粒共培养时, 细胞内铁含量随着代数的增加而减少, 但在组装体上培养的不同代数的细胞具有相似的铁含量, 并且胞内铁含量极少. 另外, 磁感应蛋白的表达表明磁性纳米颗粒的组装体对细胞有磁效应. 该研究表明, 细胞代数的选择对研究颗粒内化实验是至关重要的, 细胞代数应该作为细胞摄取实验的一个重要考虑因素.
Co-reporter:Xiquan Zhang;Meng Cao;Jing Xing;Fei Liu;Ping Dong
Medicinal Chemistry Research 2017 Volume 26( Issue 12) pp:3395-3406
Publication Date(Web):28 August 2017
DOI:10.1007/s00044-017-2032-5
To develop topoisomerase I targeted drug candidates with sophisticated liposolubility, a series of novel camptothecin derivatives were synthesized through structure-based molecular hybridization and prodrug design approach. The compounds were used as compositions in micellar emulsion preparations, and the antiproliferative efficacy of these preparations were evaluated in two cancer cell lines (A2780s and A549) in vitro. The designed molecules were afterwards optimized for better potency by modifications at the aliphatic chain, the linker and the camptothecin-yl group to reach the optimal structure 7c (TQ-B3203), an SN-38 (camptothecin derivative, 7-ethyl-camptothecin-10-yl) containing compound. 7c showed excellent capacity of inhibiting cell proliferation with IC50 value at nanomolar level, and the potency was further confirmed in other human cancer cell lines (HT-29 and HePG2) superior to the positive reference irinotecan. 7c can be a promising candidate as antitumor drug. Its micellar emulsion preparation has succeeded in the preclinical studies and is in process for investigational new drug(IND) application.
Co-reporter:Wei Zhang; Sunling Hu; Jun-Jie Yin; Weiwei He; Wei Lu; Ming Ma; Ning Gu;Yu Zhang
Journal of the American Chemical Society 2016 Volume 138(Issue 18) pp:5860-5865
Publication Date(Web):February 26, 2016
DOI:10.1021/jacs.5b12070
The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes.
Co-reporter:Lin Fan, Yanyan Tian, Rong Yin, Doudou Lou, Xizhi Zhang, Meng Wang, Ming Ma, Shouhua Luo, Suyi Li, Ning Gu and Yu Zhang
Nanoscale 2016 vol. 8(Issue 16) pp:8553-8558
Publication Date(Web):29 Dec 2015
DOI:10.1039/C5NR08232C
Conventional immunohistochemistry is limited to subjective judgment based on human experience and thus it is clinically required to develop a quantitative immunohistochemical detection. 3,3′-Diaminobenzidin (DAB) aggregates, a type of staining product formed by conventional immunohistochemistry, were found to have a special optical property of dark-field imaging for the first time, and the mechanism was explored. On this basis, a novel immunohistochemical method based on dark-field imaging for detecting HER2 overexpressed in breast cancer was established, and the quantitative analysis standard and relevant software for measuring the scattering intensity was developed. In order to achieve a more sensitive detection, the HRP (horseradish peroxidase)-labeled secondary antibodies conjugated gold nanoparticles were constructed as nanoprobes to load more HRP enzymes, resulting in an enhanced DAB deposition as a dark-field label. Simultaneously, gold nanoparticles also act as a synergistically enhanced agent due to their mimicry of enzyme catalysis and dark-field scattering properties.
Co-reporter:Ke Hu, Naizhen Zhou, Yang Li, Siyu Ma, Zhaobin Guo, Meng Cao, Qiying Zhang, Jianfei Sun, Tianzhu Zhang, and Ning Gu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 24) pp:15113-15119
Publication Date(Web):June 3, 2016
DOI:10.1021/acsami.6b04112
Cell-adhesive properties are of great significance to materials serving as extracellular matrix mimics. Appropriate cell-adhesive property of material interface can balance the cell–matrix interaction and cell–cell interaction and can promote cells to form 3D structures. Herein, a novel magnetic polyacrylamide (PAM) hydrogel fabricated via combining magnetostatic field induced magnetic nanoparticles assembly and hydrogel gelation was applied as a multicellular spheroids culturing platform. When cultured on the cell-adhesive microarray interface of sliced magnetic hydrogel, normal and tumor cells from different cell lines could rapidly form multicellular spheroids spontaneously. Furthermore, cells which could only form loose cell aggregates in a classic 3D cell culture model (such as hanging drop system) were able to be promoted to form multicellular spheroids on this platform. In the light of its simplicity in fabricating as well as its effectiveness in promoting formation of multicellular spheroids which was considered as a prevailing tool in the study of the microenvironmental regulation of tumor cell physiology and therapeutic problems, this composite material holds promise in anticancer drugs or hyperthermia therapy evaluation in vitro in the future.
Co-reporter:Fang Yang, Mingxi Li, Yang Liu, Tuantuan Wang, Zhenqiang Feng, Huating Cui, Ning Gu
Journal of Controlled Release 2016 Volume 228() pp:87-95
Publication Date(Web):28 April 2016
DOI:10.1016/j.jconrel.2016.03.002
Stimuli-responsive devices that deliver drugs or imaging contrast agents in spatial-, temporal- and dosage-controlled fashions have emerged as the most promising and valuable platform for targeted and controlled drug delivery. However, implementing high performance of these functions in one single delivery carrier remains extremely challenging. Herein, we have developed a sequential strategy for developing glucose and magnetic-responsive microvesicle delivery system, which regulates the glucose levels and spatiotemporally controls the generation of nitric oxide gas free bubbles. It is observed that such injectable microvesicles loaded with enzyme and magnetic nanoparticles can firstly regulate hyperglycemic level based on the enzymatic reactions between glucose oxidase and glucose. In a sequential manner, concomitant magnetic field stimuli enhance the shell permeability while prompts the reaction between H2O2 and l-arginine to generate the gasotransmitters nitric oxide, which can be imaged by ultrasound and further delivered for diabetic nephropathy therapy. Therefore, magnetic microvesicles with glucose oxidase may be designed as a novel theranostic approach for restoring glucose homeostasis and spatiotemporally control NO release for maintaining good overall diabetic health.Magnetic microvesicles loaded with glucose oxidase and magnetic nanoparticles are designed as a novel theranostic system to spatiotemporally control the generation of nitric oxide for restoring glucose homeostasis.
Co-reporter:Dandan Sun, Xubo Lin, Zuoheng Zhang, and Ning Gu
The Journal of Physical Chemistry C 2016 Volume 120(Issue 33) pp:18803-18810
Publication Date(Web):August 3, 2016
DOI:10.1021/acs.jpcc.6b04086
Lipid-shelled nanobubbles have shown great potential in drug and gene therapy. To improve our understanding of the ultrasound-mediated interactions of lipid nanobubbles with plasma membranes at the molecular level, we investigated the effect of shock-induced lipid nanobubble collapse on a lipid bilayer using coarse-grained molecular dynamics simulations. We observed the collapse of lipid nanobubbles and the formation of water nanojets. The water nanojets could induce structural changes in membranes. When shock velocities were sufficiently high, the deformed bilayers were hemispherical and water pores were generated. Both the nanojets and the membrane deformations depended on the shock velocity and the initial lipid nanobubble diameter. In the recovery simulations, the bilayers were able to heal themselves, indicating that the bilayer poration was temporary. Besides, compared with the cases of vacuum nanobubbles, the lipid nanobubbles could weaken the effects of shock waves. All this molecular-level information from simulations will be useful for improving the biomedical applications of lipid nanobubbles.
Co-reporter:Lina Song, Chao Huang, Wei Zhang, Ming Ma, Zhongwen Chen, Ning Gu, Yu Zhang
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2016 Volume 506() pp:747-755
Publication Date(Web):5 October 2016
DOI:10.1016/j.colsurfa.2016.07.037
A simple method to prepare GO-Fe2O3 hybrids was developed.The enzyme mimetic activity of Fe2O3 nanoparticles was effectively improved by simply introducing GO to form GO-Fe2O3 hybrids.The GO-Fe2O3 hybrids act as a pH-dependent dual-enzyme.GO-Fe2O3 hybrids exhibit the ability to degrade Rhodamine B.Graphene based materials are widely used in energy conversation and catalytic reaction due to their rapid electron transfer capacity and large surface area. Herein, graphene Fe2O3 (GO-Fe2O3) hybrids with enhanced peroxidase-like activity were fabricated. Enhanced peroxidase-like activity strongly depending on pH, temperature and hybrid concentration was observed and the peroxidase-like behavior fits well the Michaelis-Menten kinetic model. Free radicals, such as OH and O2⿿, as intermediates in the hybrid-H2O2 reaction system were directly demonstrated by electron spin resonance (ESR) technique and the selective radical inhibition experiments. Furthermore, it was found that the addition of TMB rapidly consumed OH and O2⿿, and subsequently leaded to the formation of blue TMB radical confirmed by the ESR and absorption spectroscopy. Besides acting as mimetic peroxidase in acidic buffer, the GO-Fe2O3 hybrids also displayed the enhanced catalase-like activity in neutral and alkaline buffers compared with individual Fe2O3 nanoparticles and GO sheet, respectively. The H2O2 decomposition catalyzed by the hybrids was demonstrated by ESR and the generated O2 was measured using the dissolved oxygen electrode. All the results above demonstrate that the GO-Fe2O3 hybrids are a kind of effective pH-dependent mimetic dual-enzyme.
Co-reporter:Xuan Liu 刘璇;Jie Zhang 张捷;Shijia Tang 唐诗佳;Jianfei Sun 孙剑飞
Science China Materials 2016 Volume 59( Issue 11) pp:901-910
Publication Date(Web):2016 November
DOI:10.1007/s40843-016-5104-9
Magnetic field has been considered to have positive effect on growth of bone. Because amagnetic nanoparticle can be regarded as one magnetic dipole, the macroscopic assemblies of magnetic nanoparticles may exhibit magnetic effect on local objects. This paper fabricated macroscopic film of γ-Fe2O3 nanoparticles by layer-by-layer (LBL) assembly on poly-D,L-lactic acid (PLA) scaffold, and studied the magnetic effect of the assembled γ-Fe2O3 nanoparticles film on primary bone marrow cells. The primary bone marrow cells were extracted from a mouse and cultured on the PLA substrate decorated by the film of γ-Fe2O3 nanoparticles after purification. Quantitative PCR (q-PCR) was used to show the cellular effect quantitatively. A just-found magnetosensing protein was employed to verify the magnetic effect of assembled film of nanoparticles on primary cells. It was exhibited that the decoration of nanoparticles enhanced themechanical property of the interface. By acting as the adhesion sites, the LBL-assembled film of nanoparticles seemed beneficial to the cellular growth and differentiation. The expression of magnetosensing protein indicated that there was magnetic effect on the cells which resulted from the assembly of magnetic nanoparticles, implying its potential as a promising interface on scaffold which can integrate the physical effect with good biocompatibility to enhance the growth and differentiation of stem cells. The LBL-assembled film of magnetic nanoparticles may boost the development of novel scaffold which can introduce the physical stimulus into local tissue in vivo.磁场一直以来都被认为对骨生长具有促进作用. 磁性纳米颗粒可以被看作是一个磁偶极子, 因此宏观的磁性纳米颗粒组装膜也可 能对附近的物体具有磁效应. 本文通过层层自组装方法在聚乳酸支架表面制备了宏观γ-Fe2O3纳米颗粒组装膜, 研究了γ-Fe2O3纳米颗粒组 装膜对原代小鼠骨髓细胞的磁作用. 原代小鼠骨髓细胞从小鼠体内新鲜提取, 并在前述生物材料表面培养. 定量PCR用来定量表征细胞效 应, 磁场的影响通过检测一种刚刚发现的磁感应蛋白来指示. 结果表明, 表面纳米颗粒组装可以显著增强聚合物支架的力学性质, 促进细 胞生长和分化. 磁感应蛋白检测结果表明这是由于磁性纳米颗粒组装导致的磁效应引起的. 本文用磁感应蛋白证明了磁性纳米颗粒层层 自组装膜可以通过对细胞的磁效应促进干细胞的生长和分化, 该磁性纳米颗粒组装膜将会促进新一代组织工程支架的研发, 有可能将物 理刺激效应引入到体内局部组织修复中.
Co-reporter:Gaoxin Zhou, Lushen Li, Jing Xing, Shivakumar Jalde, Yan Li, Jin Cai, Junqing Chen, Peidang Liu, Ning Gu, Min Ji
Colloids and Surfaces B: Biointerfaces 2016 Volume 148() pp:518-525
Publication Date(Web):1 December 2016
DOI:10.1016/j.colsurfb.2016.09.033
•A novel redox-responsive cerasome for tumor-targeted drug delivery.•The CFL comprises a cleavable disulfide bond was synthesized and characterized.•The EE and DLC of DOX in RRC was 74.3% and 2.4%, respectively.•Accelerated DOX release in the presence of 10 mM GSH (from 34.4% to 79.8%, 48 h).•DOX/RRCs showed effective cytotoxicity against SMCC-7721 and MCF-7 cells.Cerasome is a freshly developped bilayer vehicle that resemble traditional liposome but has higher mophorlogical stability. In this study, a novel redox-responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method. RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes. In addition, in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile: accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in the presence of 10 mM of GSH. Under the same condition, the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results. RRC showed non-toxic to human embryonic kidney 293 cells, indicating that this material has good biocompatibility. On the other hand, DOX/RRCs showed a resemble IC50 (half inhibitory concentration) value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells. IC50 values at 48 h were found to decrease in the following order: DOX/RIC > DOX/RRC > DOX. Taken together, the RRC developped in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery.
Co-reporter:Qiwei Wang, Bo Chen, Meng Cao, Jianfei Sun, Hao Wu, Peng Zhao, Jing Xing, Yan Yang, Xiquan Zhang, Min Ji, Ning Gu
Biomaterials 2016 86() pp: 11-20
Publication Date(Web):April 2016
DOI:10.1016/j.biomaterials.2016.02.004
Iron oxide nanoparticles (IONPs) are generally used in multiple biomedical applications. The tissue repair effect of IONPs had been demonstrated in the previous studies of our group, but the underlying mechanism is unclarified. It is well known that stem cell-based therapies show promising prospect in tissue engineering and regenerative medicine, however, whether IONPs could modulate stem cell fate to promote tissue repair is still unclear. Herein, we found that IONPs could promote osteogenic differentiation of human bone-derived mesenchymal stem cells (hBMSCs) in vitro. To insightfully understand the molecular mechanisms, we performed systematic analyses by use of gene microarray assay and bioinformatics analysis, which revealed that gene expression was widely regulated and classical mitogen-activated protein kinase (MAPK) signal pathway was activated by IONPs treatment. As a result, downstream genes of this pathway were regulated to promote osteogenic differentiation. In summary, the present study elucidates a molecular basis explaining how IONPs effect on hBMSCs, which could have many meaningful impacts for stem cells application in regenerative medicine.
Co-reporter:Ke Hu;Jianfei Sun;Zhaobin Guo;Peng Wang;Qiang Chen;Ming Ma
Advanced Materials 2015 Volume 27( Issue 15) pp:2507-2514
Publication Date(Web):
DOI:10.1002/adma.201405757
Co-reporter:Fang Yang, Xiaoxian Zhang, Lina Song, Huating Cui, John N. Myers, Tingting Bai, Ying Zhou, Zhan Chen, and Ning Gu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 18) pp:9410
Publication Date(Web):April 16, 2015
DOI:10.1021/acsami.5b02210
Uniform and multifunctional poly(lactic acid) (PLA)–nanoparticle composite has enormous potential for applications in biomedical and materials science. A detailed understanding of the surface and interface chemistry of these composites is essential to design such materials with optimized function. Herein, we designed and investigated a simple PLA–magnetic nanoparticle composite system to elucidate the impact of nanoparticles on the degradation of polymer–nanoparticle composites. In order to have an in-depth understanding of the mechanisms of hydrolysis in PLA–nanoparticle composites, degradation processes were monitored by several surface sensitive techniques, including scanning electron microscopy, contact angle goniometry, atomic force microscopy, and sum frequency generation spectroscopy. As a second-order nonlinear optical technique, SFG spectroscopy was introduced to directly probe in situ chemical nature at the PLA–magnetic nanoparticle composite/aqueous interface, which allowed for the delineation of molecular mechanisms of various hydrolysis processes for degradation at the molecular level. The best PLA–NP material, with a concentration of 20% MNP in the composite, was found to enhance the drug release rate greater than 200 times while maintaining excellent controlled drug release characteristics. It was also found that during hydrolysis, various crystalline-like PLA domains on the surfaces of PLA–nanoparticle composites influenced various hydrolysis behaviors of PLA. Results from this study provide new insight into the design of nanomaterials with controlled degradation and drug release properties, and the underlined molecular mechanisms. The methodology developed in this study to characterize the polymer–nanoparticle composites is general and widely applicable.Keywords: composite; controlled drug release; interface hydrolysis; nanoparticles; poly(lactic acid); sum frequency generation;
Co-reporter:Jun Dai, Junfeng Lu, Fang Wang, Jiyuan Guo, Ning Gu, and Chunxiang Xu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 23) pp:12655
Publication Date(Web):May 26, 2015
DOI:10.1021/acsami.5b03069
Screw dislocation plays a critical role in crystal growth and significantly affects the carrier dynamics process of luminescent semiconductor materials. In this paper, we report a novel screw-dislocation-induced ZnO:Sn hillock microstructure. The detailed growth process and possible formation mechanism of screw dislocation are demonstrated. The temperature-dependent photoluminescence reveals the free exciton recombination emission mechanism of the ZnO:Sn hillock microstructure. By comparing time-resolved photoluminescence spectra with those of two other samples without screw dislocations, it is found that the screw dislocation in the ZnO:Sn microstructures effectively decreases the carrier lifetime. In addition, UV Fabry–Perot lasing action is observed from the ZnO:Sn hillock microstructure, and the numerical simulation of the standing wave pattern and light intensity distribution further confirm the Fabry–Perot lasing mechanism. Therefore, ZnO:Sn can be utilized as a UV laser gain medium, and its optical properties can be modulated by screw dislocation.Keywords: carrier dynamics; lasing; photoluminescence; screw dislocation; ZnO;
Co-reporter:Jilai Tian, Fang Yang, Huating Cui, Ying Zhou, Xiaobo Ruan, and Ning Gu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 48) pp:26579
Publication Date(Web):November 16, 2015
DOI:10.1021/acsami.5b07778
Nanobubbles with a size less than 1 μm could make a promising application in ultrasound molecular imaging and drug delivery. However, the fabrication of stable gas encapsulation nanobubbles is still challenging. In this study, a novel method for preparation of lipid- encapsulated nanobubbles was reported. The dispersed phospholipid molecules in the prefabricated free nanobubbles solution can be assembled to form controllable stable lipid encapsulation gas-filled ultrasound-sensitive liposome (GU-Liposome). The optimized preparation parameters and formation mechanism of GU-Liposome were investigated in detail. Results showed that this type of GU-Liposome had mean diameter of 194.4 ± 6.6 nm and zeta potential of −25.2 ± 1.9 mV with layer by layer self-assembled lipid structure. The acoustic imaging analysis in vitro indicated that ultrasound imaging enhancement could be acquired by both perfusion imaging and accumulation imaging. The imaging enhancement level and duration time was related with the ratios of lipid to gas in the GU-Liposome structure. All in all, by this novel and controllable nanobubble construction technique, it will broaden the future theranostic applications of nanobubbles.Keywords: assembly; liposome; nanobubbles; theranostic; ultrasound imaging
Co-reporter:Lei Duan, Fang Yang, Lina Song, Kun Fang, Jilai Tian, Yijun Liang, Mingxi Li, Ning Xu, Zhongda Chen, Yu Zhang and Ning Gu
Soft Matter 2015 vol. 11(Issue 27) pp:5492-5500
Publication Date(Web):28 May 2015
DOI:10.1039/C5SM00864F
Magnetic microbubbles (MMBs) consisting of microbubbles (MBs) and magnetic nanoparticles (MNPs) were synthesized for use as novel markers for improving multifunctional biomedical imaging. The MMBs were fabricated by assembling MNPs in different concentrations on the surfaces of MBs. The relationships between the structure, magnetic properties, stability of the MMBs, and their use in magnetic resonance/ultrasound (MR/US) dual imaging applications were determined. The MNPs used were NPs of 3-aminopropyltriethoxysilane (APTS)-functionalized superparamagnetic iron oxide γ-Fe2O3 (SPIO). SPIO was assembled on the surfaces of polymer MBs using a “surface-coating” approach. An analysis of the underlying mechanism showed that the synergistic effects of covalent coupling, electrostatic adsorption, and aggregation of the MNPs allowed them to be unevenly assembled in large amounts on the surfaces of the MBs. With an increase in the MNP loading amount, the magnetic properties of the MMBs improved significantly; in this way, the shell structure and mechanical properties of the MMBs could be modified. For surface densities ranging from 2.45 × 10−7 μg per MMB to 8.45 × 10−7 μg per MMB, in vitro MR/US imaging experiments showed that, with an increase in the number of MNPs on the surfaces of the MBs, the MMBs exhibited better T2 MR imaging contrast, as well as an increase in the US contrast for longer durations. In vivo experiments also showed that, by optimizing the structure of the MMBs, enhanced MR/US dual-modality image signals could be obtained for mouse tumors. Therefore, by adjusting the shell composition of MBs through the assembly of MNPs in different concentrations, MMBs with good magnetic and acoustic properties for MR/US dual-modality imaging contrast agents could be obtained.
Co-reporter:Meng Cao;Fangzhou Liu;Xiquan Zhang;Ming Zheng;Ziqi Ye
Science China Materials 2015 Volume 58( Issue 8) pp:640-648
Publication Date(Web):2015 August
DOI:10.1007/s40843-015-0073-y
Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized compound may be inactivated before getting access to the nucleus where cisplatin forms a complex with the genomic DNA and triggers a cell death program. However, the nature and intracellular fate of inactivated cisplatin is poorly illustrated. In the present study, we reported for the first time the presence of platinum nanoparticles (Pt-NPs) in the cytoplasm of cells treated with cisplatin. Further analysis also evidenced a correlation of the increased intracellular Pt-NPs formation with cisplatin resistance, and confirmed the process was glutathione S-transferase relevant. Our data suggest that tumor cells may develop cisplatin resistance by converting the drug into less toxic intracellular Pt-NPs, thereby impeding the drug from targeting its substrates.长期使用顺铂治疗的肿瘤患者容易产生肿瘤细胞耐药性, 影响顺铂的临床治疗效果. 顺铂进入肿瘤细胞后, 在到达靶向细胞 核之前可能会失去活性, 失活后的药物将无法与DNA络合以杀伤细胞, 这是细胞产生药物耐受性的可能机制之一. 然而失活后的顺铂 在细胞内以何种形式存在这一问题尚没有得到完全阐明. 本论文研究发现, 顺铂治疗后的细胞中有铂纳米颗粒存在, 而且该类颗粒的 形成与细胞对顺铂的耐药性有一定的关系. 进一步研究发现细胞内谷胱甘肽转移酶可能在这一机制中起到了重要作用. 数据表明, 细 胞可能通过将高细胞毒性的顺铂转化为低毒性的铂纳米颗粒, 起到阻止顺铂靶向其底物的作用.
Co-reporter:Tingting Bai
The Journal of Physical Chemistry C 2015 Volume 119(Issue 51) pp:28597-28604
Publication Date(Web):November 30, 2015
DOI:10.1021/acs.jpcc.5b10095
Co-reporter:Xubo Lin;Yi Y. Zuo
Science China Materials 2015 Volume 58( Issue 1) pp:28-37
Publication Date(Web):2015 January
DOI:10.1007/s40843-014-0018-5
The interactions with the pulmonary surfactant, the initial biological barrier of respiratory pathway, determine the potential therapeutic applications and toxicological effects of inhaled nanoparticles (NPs). Although much attention has been paid to optimize the physicochemical properties of NPs for improved delivery and targeting, shape effects of the inhaled NPs on their interactions with the pulmonary surfactant are still far from clear. Here, we studied the shape effects of NPs on their penetration abilities and structural disruptions to the dipalmitoylphosphatidylcholine (DPPC) monolayer (being model pulmonary surfactant film) using coarse-grained molecular dynamics simulations. It is found that during the inspiration process (i.e., surfactant film expansion), shape effects are negligible. However, during the expiration process (i.e., surfactant film compression), NPs of different shapes show various penetration abilities and degrees of structural disruptions to the DPPC monolayer. We found that rod-like NPs showed the highest degree of penetration and the smallest side-effects to the DPPC monolayer. Our results may provide a useful insight into the design of NPs for respiratory therapeutics.肺表面活性剂是纳米颗粒经呼吸途径进入人体的初始生物屏障, 纳米颗粒与肺表面活性剂的相互作用直接决定纳米颗粒潜在的诊疗应用和毒性. 虽然已有很多研究致力于优化纳米颗粒的理化性质以提高其输运和靶向特性, 但是纳米颗粒的形状效应对其与肺表面活性剂相互作用的影响仍鲜有报道. 本文我们运用粗粒度分子动力学的方法研究了纳米颗粒的形状效应对其与一种模型肺表面活性剂—DPPC磷脂单分子层膜的作用的影响. 研究结果表明: 吸气过程中(磷脂单分子层膜扩张过程), 形状效应基本可以忽略; 呼气过程中(磷脂单分子层膜压缩过程⊠, 不同形状的纳米颗粒表现出不同的跨膜能力⊠对膜的结构扰动亦有所不同, 其中棒状纳米颗粒具有最强的跨膜能力、同时对膜的结构扰动也最小. 我们的研究结果对促进纳米颗粒的呼吸诊疗应用具有积极的作用.
Co-reporter:Ning Gu
Science China Materials 2015 Volume 58( Issue 12) pp:913-914
Publication Date(Web):2015 December
DOI:10.1007/s40843-015-0105-7
Gene therapy is known highly effective for treatment of many diseases; however, its wide use has been severely bottlenecked by lack of safe and effective delivery vectors. Cationic polymers are safe nonviral gene vectors with great potential for large-scale applications, and widely used to condense the large macromolecules into cationic polymer/DNA complexes (polyplexes) nanoparticles, protecting them from degradation and facilitating their cellular internalization. However, once inside the cells, unzipping the cationic polymer/DNA complexes is against the strong electrostatic interaction and thus intracellular release of free DNA for transcription is the main barrier to efficient DNA transfection. In a recent online publication of Advanced Materials, Professor Youqing Shen from Zhejiang University reports a very motivating design of reactive oxygen species (ROS)-labile charge-reversal polymer-based fusogenic lipidic polyplexes (FLPPs), which are promising to successfully overcome these problems.
Co-reporter:Fang Yang;Mingxi Li;Huating Cui;Tuantuan Wang;Zhongwen Chen
Science China Materials 2015 Volume 58( Issue 6) pp:467-480
Publication Date(Web):2015 June
DOI:10.1007/s40843-015-0059-9
Engineered iron oxide magnetic nanoparticles (MNPs) are one of the most promising tools in nanomedicine-based diagnostics and therapy. However, increasing evidence suggests that their specific delivery efficiency and potential long-term cytotoxicity remain a great concern. In this study, using 12 nm γ-Fe2O3 MNPs, we investigated three types of uptake pathways for MNPs into HepG2 cells: (1) a conventional incubation endocytic pathway; (2) MNPs co-administrated with microbubbles under ultrasound exposure; and (3) ultrasound delivery of MNPs covalently coated on the surface of microbubbles. The delivery efficiency and intracellular distribution of MNPs were evaluated, and the cytotoxicity induced by reactive oxygen species (ROS) was studied in detail. The results show that MNPs can be delivered into the lysosomes via classical incubation endocytic internalization; however, microbubbles and ultrasound allow the MNPs to pass through the cell membrane and enter the cytosol via a non-internalizing uptake route much more evenly and efficiently. Further, these different delivery routes result in different ROS levels and antioxidant capacities, as well as intracellular glutathione peroxidase activity for HepG2 cells. Our data indicate that the microbubble–ultrasound treatment method can serve as an efficient cytosolic delivery strategy to minimize long-term cytotoxicity of MNPs.磁性纳米颗粒在纳米生物医学诊断和治疗研究领域是极具潜力的一种纳米材料. 如何实现纳米颗粒在特定细胞或靶器官的高效率传输以及如何降低细胞毒性是目前纳米材料研究的重点内容. 本文首先研究了12 nm的γ-Fe2O3磁性纳米颗粒进入细胞的三种不同途径: (1) 纳米颗粒与肿瘤细胞共孵育后的内吞途径; (2) 纳米颗粒与微气泡共混合后超声辐照传输途径; (3) 纳米颗粒化学偶联到微气泡膜壳表面后超声辐照传输途径. 其次, 基于上述三种不同的纳米颗粒传输途径, 对纳米颗粒引起的细胞氧化应激毒性进行了深入研究. 结果表明, 纳米颗粒与肿瘤细胞共孵育后的内吞途径使纳米颗粒通过溶酶体包裹进入细胞; 通过超声微气泡辐照, 纳米颗粒能够以更高效率通过非内吞途径直接传输进入细胞质而不被溶酶体包裹. 不同传输途径导致纳米颗粒分别进入溶酶体和细胞质, 造成对细胞内氧化应激水平、总抗氧化能力以及谷胱甘肽过氧化物酶活性的响应不同. 综上研究表明, 超声微气泡介导的磁性纳米颗粒传输能够成为一种高效无损的细胞纳米颗粒输运新方法, 同时通过控制纳米颗粒进入细胞质降低了纳米颗粒的毒性, 从而能够更广泛应用于纳米生物医学的应用研究.
Co-reporter:Mo Hou;Chunxiao Chen;Dalin Tang;Shouhua Luo;Fang Yang
BioMedical Engineering OnLine 2015 Volume 14( Issue 1 Supplement) pp:
Publication Date(Web):2015 January
DOI:10.1186/1475-925X-14-S1-S14
As a dual-modality contrast agent, magnetic microbubbles (MMBs) can not only improve contrast of ultrasound (US) image, but can also serve as a contrast agent of magnetic resonance image (MRI). With the help of MMBs, a new registration method between US image and MRI is presented.In this method, MMBs were used in both ultrasound and magnetic resonance imaging process to enhance the most important information of interest. In order to reduce the influence of the speckle noise to registration, semi-automatic segmentations of US image and MRI were carried out by using active contour model. After that, a robust optical flow model between US image segmentation (floating image) and MRI segmentation (reference image) was built, and the vector flow field was estimated by using the Coarse-to-fine Gaussian pyramid and graduated non-convexity (GNC) schemes.Qualitative and quantitative analyses of multiple group comparison experiments showed that registration results using all methods tested in this paper without MMBs were unsatisfactory. On the contrary, the proposed method combined with MMBs led to the best registration results.The proposed algorithm combined with MMBs contends with larger deformation and performs well not only for local deformation but also for global deformation. The comparison experiments also demonstrated that ultrasound-MRI registration using the above-mentioned method might be a promising method for obtaining more accurate image information.
Co-reporter:Guang Li;Shouhua Luo;Yuling Yan
BioMedical Engineering OnLine 2015 Volume 14( Issue 1 Supplement) pp:
Publication Date(Web):2015 January
DOI:10.1186/1475-925X-14-S1-S15
The high-resolution X-ray imaging system employing synchrotron radiation source, thin scintillator, optical lens and advanced CCD camera can achieve a resolution in the range of tens of nanometers to sub-micrometer. Based on this advantage, it can effectively image tissues, cells and many other small samples, especially the calcification in the vascular or in the glomerulus. In general, the thickness of the scintillator should be several micrometers or even within nanometers because it has a big relationship with the resolution. However, it is difficult to make the scintillator so thin, and additionally thin scintillator may greatly reduce the efficiency of collecting photons.In this paper, we propose an approach to extend the depth of focus (DOF) to solve these problems. We develop equation sets by deducing the relationship between the high-resolution image generated by the scintillator and the degraded blur image due to defect of focus first, and then we adopt projection onto convex sets (POCS) and total variation algorithm to get the solution of the equation sets and to recover the blur image.By using a 20 μm thick unmatching scintillator to replace the 1 μm thick matching one, we simulated a high-resolution X-ray imaging system and got a degraded blur image. Based on the algorithm proposed, we recovered the blur image and the result in the experiment showed that the proposed algorithm has good performance on the recovery of image blur caused by unmatching thickness of scintillator.The method proposed is testified to be able to efficiently recover the degraded image due to defect of focus. But, the quality of the recovery image especially of the low contrast image depends on the noise level of the degraded blur image, so there is room for improving and the corresponding denoising algorithm is worthy for further study and discussion.
Co-reporter:Dawei Guo, Dandan Dou, Lin Ge, Zhihai Huang, Liping Wang, Ning Gu
Colloids and Surfaces B: Biointerfaces 2015 Volume 134() pp:229-234
Publication Date(Web):1 October 2015
DOI:10.1016/j.colsurfb.2015.06.070
•Silver nanoparticles (AgNPs) were synthesized using caffeic acid as reducing agent and stabilizer.•AgNPs with uniform size are stably in the colloidal solution.•AgNPs could enter cells via endocytosis, localize in endosomes and induce cytotoxicity toward human hepatoma HepG2 cells in a dose-dependent manner.•Apoptosis mediated cell death induced by AgNPs.Green synthesis, especially in biological processes, has gained more attention with increasing application of silver nanoparticles (AgNPs) in biomedical fields. However, the biologically synthesized AgNPs have been to be anomalous in size and shape in most cases, as well as exhibiting certain difficulties when used in therapy. We used caffeic acid, a naturally plant polyphenol, to prepare the AgNPs in the current study and also evaluated their anti-cancer activity against the human hepatoma HepG2 cells. Results showed that the AgNPs could rapidly and simply be synthesized using caffeic acid as both a reducing agent and stabilizer. The synthesized AgNPs possessed characteristics of having small size, narrow distribution and high surface negative charge, as well as being stable in aqueous solution. Furthermore, the AgNPs could enter cells and effectively inhibit viability of tumor cells via induction of apoptosis. In conclusion, a caffeic acid mediated facile method was successfully developed to prepare the AgNPs as a potential alternative agent for human hepatoma therapy.
Co-reporter:Dawei Guo, Junren Zhang, Zhihai Huang, Shanxiang Jiang, Ning Gu
Colloids and Surfaces B: Biointerfaces 2015 Volume 126() pp:198-203
Publication Date(Web):1 February 2015
DOI:10.1016/j.colsurfb.2014.12.023
•AgNPs were prepared by a continuously flow electrochemical process.•AgNPs could localize in lysosomes, mitochondria and cytoplasm of SHI-1 cells.•AgNPs together with 4-HPR showed the synergistic inhibition against SHI-1 cells.•AgNPs combined with 4-HPR induced the higher levels of ROS compared to that alone.•Silver ions were released from AgNPs in lysosome-like acidic conditions.Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy.
Co-reporter:Kun Fang, Lina Song, Zhuxiao Gu, Fang Yang, Yu Zhang, Ning Gu
Colloids and Surfaces B: Biointerfaces 2015 Volume 136() pp:712-720
Publication Date(Web):1 December 2015
DOI:10.1016/j.colsurfb.2015.10.014
•The DOX-MMS, in which DOX was encapsulated in the core and γ-Fe2O3 were coated on the surface of microsphere, were prepared.•The cumulative drug release from DOX-MMS was significantly enhanced under an external magnetic field.•The magnetic responsive DOX-MMS were designed for chemo-thermal therapy.Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.
Co-reporter:Hao Wu, Jun Lin, Peidang Liu, Zhihai Huang, Peng Zhao, Haizhen Jin, Cailian Wang, Longping Wen, Ning Gu
Biomaterials 2015 62() pp: 47-57
Publication Date(Web):
DOI:10.1016/j.biomaterials.2015.05.033
Co-reporter:Xubo Lin, Tingting Bai, Yi Y. Zuo and Ning Gu
Nanoscale 2014 vol. 6(Issue 5) pp:2759-2767
Publication Date(Web):06 Dec 2013
DOI:10.1039/C3NR04163H
Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air–water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.
Co-reporter:Tingting Bai, Jianfei Sun, Renchao Che, Lina Xu, Chenyue Yin, Zhirui Guo, and Ning Gu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 5) pp:3331
Publication Date(Web):February 17, 2014
DOI:10.1021/am405357v
Recent studies have conclusively shown that the plasmonic performance of Au nanostructures can be enhanced by incorporating Ag. Here, we developed a simple and robust approach for preparing core–shell Au–Ag nanoshuttles (NSs) using single-crystal Au nanorods (NRs) as cores. Upon tailoring the temperature of the reaction system containing alkaline glycine buffer (pH 8.5), exceptionally monodisperse Au–Ag NSs with sharp tips and tunable shell thickness could be routinely achieved in high yield through an epitaxial growth process. In particular, high-resolution transmission electron microscopy and nitric acid corrosive experiments revealed that the shells of these NSs consisted of a homogeneous Au–Ag alloy, rather than pure Ag or Au as previously reported. It was found that glycine played an important role in determining the final metal contents of the shell by regulating the reduction kinetics. In addition, the obatined Au–Ag NSs with sharp tips were shown to have significantly improved refractive index sensitivity and surface-enhanced Raman scattering activity relative to the original Au NRs, making these materials promising for biomedical applications, such as biosensing and biolabeling.Keywords: Ag; Au; core−shell structure; nanorods; refractive index sensitivity; shape control; surface-enhanced Raman scattering;
Co-reporter:Zhaobin Guo, Ke Hu, Jianfei Sun, Tianzhu Zhang, Qiying Zhang, Lina Song, Xizhi Zhang, and Ning Gu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 14) pp:10963
Publication Date(Web):July 3, 2014
DOI:10.1021/am5023946
For mimicking the fibrous extracellular matrix (ECM), a facile method for patterning anticell adhesive substrate was novelly applied on agarose hydrogel. Without using masks or templates for etching, we applied the magnetic field-induced colloidal assembly of magnetic nanoparticles on the flat agarose hydrogel to form cell-adhesive micropatterns. Meanwhile, tuning the hydrogel substrate’s modulus to fit real tissue was experimentally demonstrated. Magnetic nanobeads were also assembled on this hydrogel surface and formed more complete and regular patterns. The patterned hydrogel substrate could actually influence behaviors of different cancer cells, including adhesion, growth, and migration.Keywords: agarose hydrogel; cell-adhesive micropatterns; magnetic nanomaterials; magnetostatic field induced assembly; tumor-associated ECM
Co-reporter:Dandan Sun, Xubo Lin and Ning Gu
Soft Matter 2014 vol. 10(Issue 13) pp:2160-2168
Publication Date(Web):14 Jan 2014
DOI:10.1039/C3SM52211C
Cholesterol plays an important role in regulating the structural properties of phospholipid membranes and further influences the permeability of molecules and nanoparticles. However, nanoparticles' translocation across phospholipid membranes in the presence of cholesterol on the molecular scale is rarely studied. Here, we performed coarse-grained molecular dynamics simulations to probe the translocation of C60, one of the most popular nanoparticles, across dipalmitoylphosphatidylcholine bilayers with different concentrations of cholesterol molecules (0–50 mol%). The results reveal that the presence of cholesterol molecules induces lower area per lipid, larger bilayer thickness, and more ordered orientation of lipid tails. The higher the concentration of cholesterol molecules, the more significant is the condensing effect of lipid bilayer as just mentioned. Besides, dynamic processes, free energy profiles and permeability coefficients further indicate that the permeability of C60 decreases with increasing cholesterol concentration, which can be explained by the condensation effect and reduced free volume. Our researches provide an explicit description of the impact of cholesterol on C60 translocation across lipid bilayers.
Co-reporter:Lin Fan, Doudou Lou, Yu Zhang and Ning Gu
Analyst 2014 vol. 139(Issue 22) pp:5660-5663
Publication Date(Web):11 Sep 2014
DOI:10.1039/C4AN01342E
A novel dual-modal cell immunodetection method based on both dark-field imaging and catalysis functions of gold nanoparticles has been established, where the Rituximab–Au conjugates were used as nanoprobes to label and image specifically the CD20 overexpressed on the surface of malignant lymphoma cells of Raji with high affinity.
Co-reporter:Fei Xiong;Caiyun Yan;Jilai Tian;Kunkun Geng;Ziyi Zhu;Lina Song;Yu Zhang;Matthew Mulvale
Journal of Pharmaceutical Sciences 2014 Volume 103( Issue 12) pp:4030-4037
Publication Date(Web):
DOI:10.1002/jps.24209
Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2O3@DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2O3@DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2O3@DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2O3@DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2O3@DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex®. Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2O3@DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2O3@DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:4030–4037, 2014
Co-reporter:Kun Fang, Fang Yang, Qiying Zhang, Tianzhu Zhang, Ning Gu
Materials Letters 2014 Volume 117() pp:86-89
Publication Date(Web):15 February 2014
DOI:10.1016/j.matlet.2013.11.101
•PLGA microspheres with or without pores were prepared by simple method.•The PEI layer on the microspheres facilitates further bioconjugation.•The porous microspheres exhibited a much higher payload of biomolecules.A modified water–oil–water double emulsion solvent evaporation method was used to prepare cationic poly (lactic-co-glycolic acid) microspheres. Polyethyleneimine in external water phase was used to stabilize the microspheres and ammonium bicarbonate in internal aqueous phase was adopted to facilitate the formation of pores. It is found that the microspheres with or without pores could be manipulated by easily adjusting the polyethyleneimine concentration. In order to understand the drug delivery potential of the porous microspheres, the model macromolecule agent, fluorescein isothiocyanate–dextran was used. The results show that the porous microspheres obtained by emulsion processing have higher absorption capability compared with non-porous ones. Therefore, the as-obtained porous microspheres could be the suitable platforms for the delivery of bioactive agents.
Co-reporter:Tianzhu Zhang, Qiying Zhang, Junsong Chen, Kun Fang, Jun Dou, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2014 Volume 452() pp:115-124
Publication Date(Web):20 June 2014
DOI:10.1016/j.colsurfa.2014.03.085
•Ovarian cancer cell line HO8910 can better grow on PLGA microspheres.•Collagen I coated PLGA microsphere promoted the adhesion and growth of HO8910 cells.•HO8910 cells grew on PLGA microspheres increased expression of E-cadherin.In this study, we prepared surface-smooth and porous poly(lactic-co-glycolic acid) (PLGA) microspheres with different diameters, different sizes of pores and different densities of pores using a simple oil/water emulsion method and varying the preparation conditions, including the molecular weight of PLGA, the components of the PLGA and the addition of porogen. The surface-smooth nonporous and porous PLGA microspheres were also further modified with collagen I. The characteristics of these PLGA microspheres, including original and collagen I-coated PLGA microspheres, were evaluated in a three-dimensional (3D) culture of ovarian cancer HO8910 cells. The HO8910 cells can growth better on original porous and collagen I-coated PLGA microspheres, and express remarkably E-cadherin. These results indicate that porous PLGA microspheres and collagen-coated PLGA microspheres are promising candidates as ovarian cancer cell culture microcarriers for pathological study and high-throughput antitumor drug screening.
Co-reporter:Zhigang Zhang;Tianzhu Zhang;Junsheng Li;Zhenling Ji;Hemei Zhou;Xuefeng Zhou
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2014 Volume 102( Issue 1) pp:
Publication Date(Web):
DOI:10.1002/jbm.b.32947
Abstract
A new type of polypropylene (PP) hernia mesh, modified with poly(l-lactic acid) (PLLA), was developed and used to repair rat abdominal wall defect. The PP mesh was first treated with oxygen plasma and then grafted with PLLA in phosphorus pentachloride (PCl5) solution in dichloride methane. The water contact angle changed during the procedure, and the coverage percentage of PLLA on the PP was about 80%. ATR-FTIR spectroscopy measurements showed the existence of carbonyl group absorption peak (1756.9 cm−1), and atomic force microscope and scanning electron microscope morphological observation indicated that the surface of the PP mesh was covered with PLLA graft. X-ray photoelectron spectroscopy spectra was used to probe chemical group changes and confirmed that the PLLA was grafted onto the PP. A total of 36 Sprague–Dawley rats were randomly divided into six groups, and they received either modified meshes (experimental groups) or PP meshes (control groups) to repair abdominal wall defects. All animals survived until the end of the experiment. Rats in each group were dissected after the operation (after 1 week, 2 weeks, and 1 month, respectively), and the adhesion effects were evaluated. Sections of the mesh parietal peritoneum overlap were examined histologically and graded for inflammation reaction. Compared with the control groups, the experimental groups showed a better ability to resist peritoneal cavity adhesions (P < 0.05), and there was no increase in inflammation formation (P > 0.05). This new type of PLLA-modified PP mesh displayed an additional property of antiadhesion in animal abdominal wall defect repair. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 12–21, 2014.
Co-reporter:Xubo Lin
Nano Research 2014 Volume 7( Issue 8) pp:1195-1204
Publication Date(Web):2014 August
DOI:10.1007/s12274-014-0482-3
Co-reporter:Xuefeng Zhou, Tianzhu Zhang, Dawei Guo, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2014 Volume 441() pp:34-42
Publication Date(Web):20 January 2014
DOI:10.1016/j.colsurfa.2013.08.070
•PU films were modified with PEO by a facile, environment-friendly approach.•The hemocompatibility of the PEO-coated PU was significantly improved.•PEO-coated PU films were very hydrophilic.•The higher molecular weight of PEO shows better hemocompatibility.Poly(ethylene oxide) (PEO) has been widely applied in the modification of biomaterials because it shows high hydrophilicity and excellent biocompatibility. In the current study, the surface of medical polyurethane (PU) films was modified to improve hydrophilicity and hemocompatibility by a facile method without catalyst. PU films were modified directly using poly(ethylene oxide) (PEO) with various molecular weights. The existence, morphology, hydrophilicity and hemocompatibility were approved and studied respectively by attenuated total reflectance infrared spectroscopy (ATR-IR), atomic force microscopy (AFM), scanning electron microscopy (SEM), contact angel measurement and platelet-rich plasma adhesion study. Compared with the raw counterpart, the PEO-modified PU films have significant improved hydrophilicity and reduced platelet adhesion, as well as less shape deformation, especially for the one modified by the PEO (Mn = 300,000). These substantial improvements indicate potential application as blood-contacting coating in medical device.
Co-reporter:Peidang Liu, Zhihai Huang, Zhongwen Chen, Ruizhi Xu, Hao Wu, Fengchao Zang, Cailian Wang and Ning Gu
Nanoscale 2013 vol. 5(Issue 23) pp:11829-11836
Publication Date(Web):29 Jul 2013
DOI:10.1039/C3NR01351K
Malignant gliomas are the most common primary intracranial tumors with a dismal prognosis. Previous investigations by our group demonstrated the radiosensitizing effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the present study was to evaluate the efficacy of intratumoral administration of AgNPs in combination with a single dose of ionizing radiation at clinically relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20 μg/10 μl) were stereotactically administered on day 8 after tumor implantation. One day after AgNP injection, rats bearing glioma received 10 Gy radiation. The mean survival times were 100.5 and 98 days, the corresponding percent increase in life spans was 513.2% and 497.7%, and the cure rates were 41.7 and 38.5% at 200 days for the 10 and 20 μg AgNPs and radiation combination groups, respectively. In contrast, the mean survival times for irradiated controls, 10 and 20 μg AgNPs alone, and untreated controls were 24.5, 16.1, 19.4, and 16.4 days, respectively. Furthermore, a cooperative antiproliferative and proapoptotic effect was obtained when gliomas were treated with AgNPs followed by radiotherapy. Our results showed the therapeutic efficacy of AgNPs in combination with radiotherapy without apparent systemic toxicity, suggesting the clinical potential of AgNPs in improving the outcome of malignant glioma radiotherapy.
Co-reporter:Fang Yang, Qing Wang, Zhuxiao Gu, Kun Fang, Gerard Marriott, and Ning Gu
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 18) pp:9217
Publication Date(Web):August 29, 2013
DOI:10.1021/am4029747
Microbubbles (MBs) coupled with nanoparticles represent a new class of multifunctional probe for multiscale biomedical imaging and drug delivery. In this study, we describe the development of multifunctional, microscale microbubble probes that are composed of a nitrogen gas core and a biocompatible polymer shell harboring silver nanoparticles (AgNPs). Ultrasound imaging studies show that the presence of AgNPs in the MB significantly improves the contrast of ultrasound images. The AgNPs within individual MB can be also imaged by using dark-field microscopy (DFM), which suggests that AgNPs in the polymer shell adopt multiple structural forms. AgNPs are released from the polymer shell following a brief exposure to an ultrasonic field and are subsequently taken up by living cells. AgNPs within labeled cells are imaged by DFM, while surface-enhanced Raman scattering is used to identify specific cytoplasmic biomolecules that bind to the surface of the AgNP. Collectively, these studies demonstrate the application of multifunctional MBs for micrometer scale contrast-enhanced ultrasound imaging, as vehicles for the ultrasound-based delivery of optical probes and drugs to cells, and for imaging of chemical sensing of individual nanopartiles within cells and tissue.Keywords: diagnostics; microstructure surface; nanoparticles; optical imaging; ultrasound imaging;
Co-reporter:Yu Wan, Zhirui Guo, Xiaoli Jiang, Kun Fang, Xiang Lu, Yu Zhang, Ning Gu
Journal of Colloid and Interface Science 2013 Volume 394() pp:263-268
Publication Date(Web):15 March 2013
DOI:10.1016/j.jcis.2012.12.037
Silver nanoparticles (AgNPs) are attracting tremendous attention in biomedicine, and their related performances are shape and size-dependent. For biomedical applications, water-soluble AgNPs are necessary. However, aqueous syntheses of AgNPs with controlled shape and size are relatively difficult as the balance between nucleation and growth is hard to regulate. This paper describes a robust method for controllable synthesis of quasi-spherical AgNPs based on the combination of the seed-mediated growth and the Lee–Meisel method by thermal reduction of AgNO3 with citrate. In the presented method, citrate-stabilized AgNPs with tunable sizes up to 80 nm were achieved through one-step or stepwise growth process using qualified spherical 4 nm AgNPs as starter seeds. Specially, the two main difficulties (formation of nanorods and secondary nucleation during the growth stage) in the previous studies have been effectively overcome by tailoring the experimental parameters such as the reaction temperature and the seed amount, without extra additives, pH adjustment, and laser treatment. The crucial factors that affect the uniformity of the resulting AgNPs are discussed.Graphical abstractHighlights► Qualified Ag nanoparticles of 4 nm were reproducibly obtained in water. ► Quasi-spherical Ag nanoparticles with controlled sizes were obtained in water. ► Formation of nanorods and secondary nucleation were effectively overcome. ► No extra additives, pH adjustment, and laser ablation are needed. ► The ratio of monomer to seed is critical to control of the final particles.
Co-reporter:Ming Ma, Jun Xie, Yu Zhang, Zhongping Chen, Ning Gu
Materials Letters 2013 Volume 105() pp:36-39
Publication Date(Web):15 August 2013
DOI:10.1016/j.matlet.2013.04.020
•Platinum modified Fe3O4 nanoparticles were prepared by a simple method.•The activity of Fe3O4@Pt NPs as peroxidase mimetics was evaluated in the TMB–H2O2 system.•Fe3O4@Pt NPs exhibited a larger Kcat value than that of Fe3O4 NPs, suggesting a higher peroxidase-like activity.Pt modified Fe3O4 magnetic nanoparticles (Fe3O4@Pt NPs) were synthesized by a simple method. The morphology and crystal structure of the as-prepared nanocomposite were characterized by TEM, XRD and EDS. The peroxidase-like catalytic activity of the synthesized nanoparticles was also investigated. Catalysis was found to follow Michaelis–Menten kinetics. The calculated kinetic parameters of the Fe3O4@Pt NPs show that they exhibited strong affinity with substrates and enhanced catalytic activity than that of Fe3O4 nanoparticles, suggesting a higher peroxidase-like activity.
Co-reporter:Tianzhu Zhang, Junsong Chen, Qiying Zhang, Jun Dou, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2013 Volume 422() pp:81-89
Publication Date(Web):5 April 2013
DOI:10.1016/j.colsurfa.2013.01.030
In this work, three kinds of poly(ethylene glycol)-cross linked poly(methyl vinyl ether-co-maleic acid) hydrogels, Gel-1, Gel-2, and Gel-3 with different elastic modulus of 105,100 Pa, 12,020 Pa, and 2191 Pa were designed for simulating respectively the mechanical strength of stiffer metastasis bone sites, cancerous soft tissue, and BME or collagen, and were evaluated in three-dimensional (3D) culture of human ovarian cancer cell line HO8910. The proliferation, adhesion, migration, and invasion of ovarian cells HO8910 in these three kinds of hydrogels were systematically investigated and compared with two commercial hydrogels BME and collagen I. Hydrogels Gel-1 and Gel-2 with higher elastic modulus showed a better cytocompatibility and remarkably supported the proliferation of ovarian cancer cell line HO8910 and the formation of multicellular spheroids (MCS) in a 3D model. The mechanical properties of hydrogels played a crucial role in responses of HO8910 cells. The hydrogels Gel-1 and Gel-2 are also the potential 3D culture matrix materials for cancer cell culture.Highlights► Ovarian cancer cell line HO8910 can form multicellular spheroids (MCS) in PEG-cross linked PMVE-co-MA hydrogel. ► Elastic modulus G′ of hydrogel can remarkably influence the proliferation of HO8910; the higher elastic modulus is more beneficial to the adhesion and proliferation of HO8910. ► PMVE-co-MA-based hydrogel is potential 3D cell culture matrix.
Co-reporter:Ning Gu;Yan Li;Meng Wang;Min Cao
Science Bulletin 2013 Volume 58( Issue 21) pp:2521-2529
Publication Date(Web):2013 July
DOI:10.1007/s11434-013-5917-9
Nano-opto-electronics for biomedicine is a developing interdisciplinary field. Related areas of this field are tried to be classified and outlined herein. Progresses in the different areas were reviewed based on the research development of the invited experts. Prospects of nano-opto-electronics for biomedicine are discussed.
Co-reporter:Jun Dou;Xiangfeng He;Yunjing Liu;Zhihai Huang
Journal of Nanoparticle Research 2013 Volume 15( Issue 12) pp:
Publication Date(Web):2013 December
DOI:10.1007/s11051-013-2127-y
Studies from hematopoietic origin malignancies have demonstrated that multiple myeloma contain a rare population of cancer stem cells (CSCs) that are responsible for tumor multiresistance and recurrence. The goal of this study was to investigate targeted therapeutic effect of anti-ABCG2 monoclonal antibody (McAb) combined with silver nanoparticles (AgNPs) and vincristine (VCR) on myeloma CSCs. The characteristics of CD44+ CD24− cells that were isolated from the SP2/0 cells using magnetic activated cell sorting system were first identified. The results showed that the CD44+ CD24− cells exhibited higher proliferation, more colony formation, more side population fraction, and stronger tumorigenicity in BALB/c mice than the control cells. Moreover, CD44+ CD24− cells markedly up-regulated the ABCG2 expression, however, anti-ABCG2 McAb combined with AgNPs and VCR effectively inhibited the CD44+ CD24− cell growth and prolonged the survival of myeloma-bearing mice. We concluded that the CD44+ CD24− cells in mouse myeloma SP2/0 cell line posses CSC properties. Anti-ABCG2 McAb combined with AgNPs and VCR provide an efficient targeted therapeutic method for inhibiting myeloma CD44+ CD24− CSC growth in mice.
Co-reporter:Meng Wang, Min Cao, Zhirui Guo, and Ning Gu
The Journal of Physical Chemistry C 2013 Volume 117(Issue 22) pp:11713-11717
Publication Date(Web):May 13, 2013
DOI:10.1021/jp4004054
Plasmon coupling in plasmonic oligomers gives rise to many unique optical properties including electromagnetically induced transparency and Fano resonances. Controlling over the optical properties of plasmonic oligomers requires a deep understanding of the physical mechanisms. Herein, we first examine the near and far field optical properties of silver pentamer by the coupled dipole approximation. It is shown that the Fano-like resonance in the pentamer is analogous to the spectrum of a heterogeneous plasmonic dimer. Therefore, we propose a subgroup decomposition method for predicting the spectrum profiles of the oligomers. In the decomposition procedure, the oligomer is divided into simple subgroups in terms of the arrangement of nanoparticles and incident polarization, and the optical response of the oligomer is determined by the coupling of the subgroups. We further investigate its validity in strongly coupled plasmonic oligomers through the generalized multiparticle Mie solution. The optical properties of the close-packed oligomers can also be easily modulated by means of the decomposition method, which provides a flexible tool for the optimal design of plasmonic nanostructures.
Co-reporter:Dawei Guo, Lingying Zhu, Zhihai Huang, Haixia Zhou, Yue Ge, Wenjuan Ma, Jie Wu, Xiuyan Zhang, Xuefeng Zhou, Yu Zhang, Yun Zhao, Ning Gu
Biomaterials 2013 34(32) pp: 7884-7894
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.07.015
Co-reporter:Fang Yang;Sunling Hu;Yu Zhang;Xiaowei Cai;Yan Huang;Feng Wang;Song Wen;Gaojun Teng
Advanced Materials 2012 Volume 24( Issue 38) pp:5205-5211
Publication Date(Web):
DOI:10.1002/adma.201202367
Co-reporter:Wen He, Fang Yang, Yihang Wu, Song Wen, Ping Chen, Yu Zhang, Ning Gu
Materials Letters 2012 Volume 68() pp:64-67
Publication Date(Web):1 February 2012
DOI:10.1016/j.matlet.2011.10.013
Microbubbles (MBs) with the ability of enhancing ultrasound image contrast and delivering drugs are widely used in medical applications. By combining microbubbles and superparamagnetic iron oxide (SPIO) nanoparticles, dual-modality contrast agent for both ultrasound and magnetic resonance (MR) imaging can be obtained. In this study, we synthesized microbubbles with a novel structure, which included a nitrogen gas core, a polymer shell, and SPIO nanoparticles on the shell surfaces. In vitro experiments showed that microbubbles with such structure provided both higher ultrasound and MR enhancement than blank microbubbles without SPIO nanoparticles and previously designed SPIO-embedded microbubbles. Furthermore because SPIO-coated microbubbles have abundant amino groups on the surface, such microbubbles have potentiality for targeted imaging after specific targeted ligands or antibodies are linked.Highlights► We report synthesis method of microbubbles (MBs) with SPIO nanoparticles on surfaces. ► SPIO-coated MBs preserve superparamagnetic properties better than SPIO-embedded MBs. ► SPIO-coated MBs have better ultrasound contrast than MBs without SPIO. ► SPIO-coated MBs have better MRI contrast than SPIO-embedded MBs.
Co-reporter:Zhirui Guo, Yu Wan, Meng Wang, Lina Xu, Xiang Lu, Guang Yang, Kun Fang, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2012 Volume 414() pp:492-497
Publication Date(Web):20 November 2012
DOI:10.1016/j.colsurfa.2012.07.034
Gold nanobipyramids (NBPs) have attracted intensive attentions because they exhibit more advantageous plasmonic properties than comparable gold nanorods. However, unlike that short gold nanorods can be synthesized routinely in a high yield (around 99% of the total particles), current syntheses of gold NBPs generally receive a low yield (around 30% of the total particles) and co-produce spherical impurities difficult to separate. Thus an effective purification route of gold NBPs is desirable for optimizing their performances. In this study, we demonstrated that the spherical nanoparticles with smaller inter-particle contact area can be separated from the NBPs that undergo gradual precipitation by electrolyte-induced electrostatic screening. During this procedure, no special surface-functionalization of the NBPs was needed. As a result of this simple separation strategy, NBPs at a level of purity to above 90% is achieved in a single purification round. In particularly, the precipitates of cetyltrimethylammonium bromide (CTAB)-capped NBPs can be easily converted into colloidal state due to the strong steric constraint of CTA+ bilayer, facilitating further investigations.Graphical abstract.Highlights► Gold nanobipyramids with a purity of over 90% were firstly reported. ► The nano-mixtures subjected to shape-selective aggregation after adding salt. ► The aggregation of nanobipyramids was reversible and the reason was discussed.
Co-reporter:Mengjie Song, Yu Zhang, Sunling Hu, Lina Song, Jinlai Dong, Zhongping Chen, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2012 Volume 408() pp:114-121
Publication Date(Web):20 August 2012
DOI:10.1016/j.colsurfa.2012.05.039
Monodisperse magnetite nanoparticles (Fe3O4 NPs) were synthesized by thermal decomposition of Fe(oleate)3 in 1-octadecene containing oleic acid. Two kinds of oleic acid capped Fe3O4 nanoparticles (Fe3O4@OA) with different shape but similar size were obtained, quasi-cubical and spherical respectively. Ligand exchange reaction with 2,3-dimercaptosuccinic acid (DMSA) was performed to transfer Fe3O4 NPs from organic phase to aqueous phase. TEM, DLS and EDS were used to characterize and evaluate these samples. TEM showed that ligand exchange reaction made the nanoparticles shape changed, especially the quasi-cubical ones. With EDS analysis, effects of surface exchange on Fe3O4@DMSA NPs were further studied. Magnetic properties, including saturation magnetization (Ms), relaxivity (r2) of Fe3O4 NPs as MRI contrast agent and specific absorption rate (SAR) in alternating magnetic field, were investigated with respect to Fe3O4 nanoparticle morphology and surface exchange time. Results showed that nanoparticles of quasi-cubical shape, obtained using shorter surface exchange time, had stronger saturation magnetization which accordingly resulted in better MRI contrast and heat conversion efficiency under magnetic induction.Graphical abstractHighlights► Magnetic Fe3O4 NPs with different shape but the same size and surface were obtained. ► Samples were monodisperse which hardly changed using longer ligand exchange time. ► Magnetism was compared based on different morphology and ligand exchange time. ► Sample surfaces were destroyed during ligand exchange, leaving magnetism weakened. ► Quasi-cubical sample had better magnetism than spherical one under comparable condition
Co-reporter:Yan Li;ZhongWen Chen
Science Bulletin 2012 Volume 57( Issue 31) pp:3972-3978
Publication Date(Web):2012 November
DOI:10.1007/s11434-012-5295-8
Magnetic nanoparticles (MNPs) have great potential for a wide use in various biomedical applications due to their unusual properties. It is critical for many applications that the biological effects of nanoparticles are studied in depth. To date, many disparate results can be found in the literature regarding nanoparticle-biological factors interactions. This review highlights recent developments in this field with particular focuses on in vitro MNPs-cell interactions. The effect of MNPs properties on cellular uptake and cytotoxicity evaluation of MNPs were discussed. Some employed methods are also included. Moreover, nanoparticle-cell interactions are mediated by the presence of proteins absorbed from biological fluids on the nanoparticle. Many questions remain on the effect of nanoparticle surface (in addition to nanoparticle size) on protein adsorption. We review papers related to this point too.
Co-reporter:Fei Xiong;Zi-yi Zhu;Chen Xiong;Xiao-qing Hua;Xiu-hong Shan
Pharmaceutical Research 2012 Volume 29( Issue 4) pp:1087-1097
Publication Date(Web):2012 April
DOI:10.1007/s11095-011-0653-9
To report a modified preparation and to systematically study the structure, magnetic and other properties of γ-Fe2O3-DMSA-DG NPs (2-deoxy-D-glucose (2-DG) conjugated meso-2,3-dimercaptosuccinic acid coated γ-Fe2O3 nanoparticles) and test its ability to improve Hela tumor cells targeting in vitro compared to the γ-Fe2O3-DMSA NPs.The conjugation of 2-DG on the surface of γ-Fe2O3-DMSA NPs was performed by esterification reaction and characterized. Acute toxicity was evaluated using MTT assay. Cellular uptake was investigated by Prussian blue staining and UV colorimetric assay.DG was successfully functionalized onto the surface of γ-Fe2O3-DMSA NPs; binding efficiency was ~60%. The mean diameter of single core of γ-Fe2O3-DMSA-DG NPs was 10 nm. Particle size and polydispersity index of its aggregates were 156.2 nm and 0.162, respectively. 2-DG-conjugated nanoparticles caused little cytotoxic effects on Hela cells at the concentration range of 0–600 μg/mL. When 2-DG-conjuated and non-conjugated nanoparticles were incubated with Hela cells for 4, 8 and 12 h, the 2-DG-conjugated nanoparticle showed significant amount of uptake in cells compared to their non-targeted counterparts.γ-Fe2O3-DMSA-DG NPs could be developed as a tumor-targeted probe for cervical cancer imaging and therapy.
Co-reporter:DaWei Guo;XiuYan Zhang;ZhiHai Huang;XueFeng Zhou
Science China Life Sciences 2012 Volume 55( Issue 10) pp:898-905
Publication Date(Web):2012 October
DOI:10.1007/s11427-012-4382-z
With the rapid development of nanotechnology and increasingly broad bio-application of engineered nanomaterials, their biohazards have become a serious public concern. It is believed that the chemical nature, particle size, morphology, and surface chemistry of nanomaterials are key parameters that influence their toxicity. Although cultured cells have been widely used to evaluate nanomaterial toxicity, it remains unclear whether the passage of these cells affects the evaluation results. In the present study, Ba/F3 cells transfected with the BCR-ABL gene were subcultured to study the effect of passage number on cell stability and their cellular responses upon exposure to nanomaterials. The results demonstrated that proliferation, cellular senescence, BCR-ABL gene expression, cell cycle and apoptosis were stable across multiple passages. Senescence and BCR-ABL gene expression of cells from different passage cells were unchanged when treated with silver nanoparticles (AgNPs). In addition, the cells at multiple passage numbers were all arrested in the G2/M phase and apoptosis was induced by the AgNPs. These nanoparticles could enter cells via endocytosis and localize in the endosomes, which were also not influenced by passage number. These data suggest that short-term passage would not affect cultured cell stability and toxicity assessment using these cells would be consistent when maintained appropriately.
Co-reporter:Jianfei Sun, Jian Dong, Dongke Sun, Zhirui Guo, and Ning Gu
Langmuir 2012 Volume 28(Issue 16) pp:6520-6526
Publication Date(Web):April 2, 2012
DOI:10.1021/la300212d
Gold nanoshells currently attract increasing research interests due to the important role in many subjects. For practical applications, random arrangement of the nanoparticles is often unfavored so that the assembly of gold nanoshells is becoming a central issue. We here proposed to utilize time-variant magnetic field to direct the assembly of gold nanoshells. It was discovered that the alternating magnetic field can mediate the vortex-like assembly of gold nanoshells. The mechanism was explored and thought to be relative with the electric field of induction which caused the thermal gradient on the substrate and the electric force. The vortexlike structure as well as the assembly mechanism will play an important role in research and application of gold nanomaterials.
Co-reporter:Xubo Lin, Changling Wang, Meng Wang, Kun Fang, and Ning Gu
The Journal of Physical Chemistry C 2012 Volume 116(Issue 33) pp:17960-17968
Publication Date(Web):August 1, 2012
DOI:10.1021/jp305784z
Supported lipid bilayer (SLB) represents a kind of well-established model cell membrane and is also used for many biosensors or biodevices. Here, for the first time, we use molecular dynamics simulation to study the effects of nanoparticle (NP) adsorption on SLB. In our simulations, the surface charge properties and the heating effects of NPs are investigated. Results show that NPs' adsorption behavior, SLB's diffusion ability, and local order parameter distribution are largely dominated by the property of the NPs' surface charge. Meanwhile the NPs' heating can increase the nearby lipids' and water's thermal motions, thus disrupting the surface charge's domination on the aforementioned properties. Besides, we find that the solid support may induce more intense thermal motions but poorer diffusion ability for the lipid leaflet closer to the support. This study provides useful insights on the NPs' disruption to the functioning of the biological membrane and the performance of SLB-based biosensors or biodevices.
Co-reporter:Zhongwen Chen, Jun-Jie Yin, Yu-Ting Zhou, Yu Zhang, Lina Song, Mengjie Song, Sunling Hu, and Ning Gu
ACS Nano 2012 Volume 6(Issue 5) pp:4001
Publication Date(Web):April 25, 2012
DOI:10.1021/nn300291r
Iron oxide nanoparticles (IONPs) are frequently used in biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they interact with hydrogen peroxide (H2O2) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H2O2-induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe3O4 and γ-Fe2O3 nanoparticles could catalyze H2O2 to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe3O4 > γ-Fe2O3, which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H2O2 into H2O and O2 directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H2O2 is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential.Keywords: catalase; cytotoxicity; ESR; hydroxyl radical; iron oxide nanoparticles; peroxidase
Co-reporter:Dongfang Liu;Wei Wu;Jingjing Ling;Song Wen;Xizhi Zhang
Advanced Functional Materials 2011 Volume 21( Issue 8) pp:1498-1504
Publication Date(Web):
DOI:10.1002/adfm.201001658
Abstract
A practical and effective strategy for synthesizing PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) is established. In this strategy, poly(acrylic acid) (PAA) is combined with SPIONs via multiple coordination between the carboxylic groups of PAA and SPIONs, which introduces abundant carboxylic groups, then, α,ω-diamino PEG is linked to SPIONs via the amidation of the carboxylic groups. The synthesized PEGylated SPIONs exhibit no cytotoxicity and high resistance to phagocytosis by macrophages in vitro as well as low uptake by the liver and spleen in vivo, which makes the SPIONs highly efficient in tumor imaging by magnetic resonance imaging (MRI) at a relatively low dose of SPIONs. These outstanding properties are largely due to the significant shielding effect of the dense PEG coating as well as the net neutral surface of the PEGylated SPIONs in physiological conditions. In summary, the PEGylated SPIONs prepared by this strategy exhibit great application potential in tumor imaging as MRI contrast agents targeting through enhanced permeability and retention (EPR) effect.
Co-reporter:Xubo Lin, Yang Li and Ning Gu
Soft Matter 2011 vol. 7(Issue 8) pp:3882-3888
Publication Date(Web):08 Mar 2011
DOI:10.1039/C0SM01382J
We have performed coarse grained molecular dynamics simulations (CGMD) to investigate the interactions of generation 7, 5 and 3 (G7, G5 and G3) charge-neutral polyamidoamine (PAMAM) dendrimers with a DPPC (dipalmitoylphosphatidylcholine) monolayer at the air–water interface (model pulmonary surfactant) during the end-expiration process. Our results show that different generations of PAMAM dendrimers have different influences on the DPPC monolayer. Generally, G3 PAMAM dendrimers show little influence on the DPPC monolayer's structure and relative properties. While G7 and G5 PAMAM dendrimers tend to induce the formation of largely deformed structures of the DPPC monolayer and inhibit or even reverse the normal phase transition of the interfacial DPPC molecules during the process of compression. Besides, we find that the formation processes of these disrupted structures are energy-favorable based on analyzing van der Waals interaction energy between PAMAM dendrimers and the whole system.
Co-reporter:Xiaoli Jiang, Tianzhu Zhang, Lina Xu, Changling Wang, Xuefeng Zhou, and Ning Gu
Langmuir 2011 Volume 27(Issue 9) pp:5410-5419
Publication Date(Web):April 6, 2011
DOI:10.1021/la200375t
Breath figure (BF) process is a facile method to prepare honeycomb structures by dynamic movements of condensed micrometer-sized water droplets at the interface of volatile fluid. Here, we aim to find answers to understand how the BF process occurs on micropipettes with curvature gradient and to understand the role of the surfactant in obtaining honeycomb patterns. Poly (l-lactic acid) (PLLA) chloroform solution with dioleoylphosphatidylethanolamine (DOPE) as surfactant was utilized. It is found that the honeycomb structure formed on the micropipettes changes remarkably with the gradually increased surface curvature. The variation trends of the arrangement and diameter of pores on the micropipettes with the increasing curvature are similar to the different time stages of BF process: smaller and sparse pores formed at higher curvature are similar to those formed at early stage of BF; regular honeycomb patterns formed at lower curvature are similar to those formed at the late stage of BF. Especially, the “semi-coalescence” hemispherical pores strings are found at high curvatures on PLLA−DOPE films, indicating the surfactant-induced coalescence of water droplets in BF process. The differences of drying speed of polymer solvent on micropipette with gradually increased curvatures make the printing of the pores at different BF stages on polymer film possible. These findings not only strongly support the mechanism of BF array formation, but also elucidate the surfactant-induced coalescence.
Co-reporter:Meng Wang ; Min Cao ; Xin Chen
The Journal of Physical Chemistry C 2011 Volume 115(Issue 43) pp:20920-20925
Publication Date(Web):September 21, 2011
DOI:10.1021/jp205736d
Subradiant plasmon modes play an important role in plasmon coupling, which can couple to the superradiant modes resulting in Fano resonances. In this study, we investigated the behaviors of the subradiant plasmons in multilayer metal–dielectric nanoshells using the generalized Mie theory. We showed that it is possible to get a pronounced Fano resonance in a single concentric nanoshell by controlling the size and geometry. The near-field coupling effects in multilayer nanoshell chains were studied by changing the alignment, particle number, and interparticle spacing. The local electric field and induced surface charge distributions were plotted to gain physical insight into the coupling mechanisms. The interactions between the particles result in a well-developed Fano resonance due to the broadening of bright plasmon modes. The subradiant plasmon modes remain robust and nearly uninfluenced by the near-field coupling and the surrounding medium. At the Fano resonance frequency, the largest field enhancement occurs in the silica layer, which is quite different from solid metal nanoparticle chains.
Co-reporter:Shiying He;Youzhi Feng;Hongxuan Ren;Yu Zhang
Journal of Soils and Sediments 2011 Volume 11( Issue 8) pp:1408-1417
Publication Date(Web):2011 December
DOI:10.1007/s11368-011-0415-7
Iron oxide magnetic nanoparticles (IOMNPs) have numerous exciting applications due to their unique chemical and physical properties. With increased applications of engineered nanostructures, releases of such materials to soil are undoubtedly inevitable. Their potential environmental risks have attracted increasing concern. One area of concern is their effect on microorganisms, which are important components of ecosystems.In this work, the effect of IOMNPs (Fe3O4 and γ-Fe2O3) on the soil bacterial community has been studied with molecular approaches and enzyme analyses. The community structure and population size were analysed using molecular-based methods, including PCR-denaturing gradient gel electrophoresis and real-time quantitative PCR based on the universal bacterial biomarker, the 16S rRNA gene sequence fragment for the bacterial variable V3 region. In addition, plate counting was conducted to validate the results of molecular methods. Four enzyme activities (dehydrogenase, urease, invertase and phosphatase) involved in cycling the main biologically important nutrients (C, N and P) were measured.Our analysis revealed that the addition of IOMNPs could potentially stimulate some bacterial growth and change the soil bacterial community structure, although bacterial abundance does not change. Based on molecular fingerprinting and sequencing analysis, several potential IOMNPs-stimulated bacteria were related to Actinobacteria, such as Duganella, Streptomycetaceae or Nocardioides. Meanwhile, soil urease and invertase activities significantly increased under IOMNPs amendment, which could be a consequence of the changes in the bacterial community.Molecular evidence suggests that IOMNP addition may facilitate C and N cycling in soil by influencing soil bacterial community. These findings are of great help towards building a comprehensive understanding of the potential impact of nanoparticles on the environment.
Co-reporter:J Dou, Y Wu, J Wang, F Zhao, L Chu, C Liu, P Wen, W Hu, K Hu, X F He and N Gu
Cancer Gene Therapy 2010 17(10) pp:675-683
Publication Date(Web):June 11, 2010
DOI:10.1038/cgt.2010.23
Previous studies have indicated that the cytokine interleukin (IL)-21 may induce both innate and adaptive immune responses against tumors. The goal of this study was to evaluate a new adoptive immunotherapy strategy that combined lymphocytes from mice immunized with a murine myeloma vaccine secreting murine IL-21 (mIL-21-Sp2/0) in lymphopenic mice induced by cyclophosphamide. The data indicate that effective antitumor immunity was induced in mice receiving syngeneic murine lymphocytes from the mice immunized with the mIL-21-Sp2/0. More importantly, the efficacy against the Sp2/0 cell challenge was enhanced after the lymphocytes were activated and proliferated ex vivo before administration into the lymphopenic mice. We conclude that the adoptive transfer of tumor antigen-specific lymphocytes into mice immunized with mIL-21-Sp2/0 induced protective immune responses against myeloma challenge.
Co-reporter:Xu Fan, Lianke Liu, Zhirui Guo, Ning Gu, Lina Xu, Yu Zhang
Materials Letters 2010 Volume 64(Issue 23) pp:2652-2654
Publication Date(Web):15 December 2010
DOI:10.1016/j.matlet.2010.08.072
Co-reporter:Xuefeng Zhou;Tianzhu Zhang;Xiaoli Jiang
Journal of Applied Polymer Science 2010 Volume 116( Issue 3) pp:1284-1290
Publication Date(Web):
DOI:10.1002/app.31499
Abstract
The medical polyurethane (PU) film was grafted with poly(acrylic acid) (PAA) to improve the hydrophilic and lubricious properties. The influences of pretreatment by ozone or potassium peroxydisulfate on themorphologies of PU films and grafting results were systematically investigated. The grafted PU films were characterized using attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM) and gel permeation chromatography (GPC). The hydrophilic and lubricious properties were evaluated by water contact angle and friction coefficient, respectively. The results showed that PAA could be grafted firmly on PU activated by both ozone and potassium peroxydisulfate, and the PAA-grafted PU showed good hydrophilic and lubricious performance. More importantly, the PAA-grafted PU films with the pretreatment of ozone were better in surface roughness, hydrophilicty and lubricity, compared to those with the pretreatment of potassium peroxydisulfate. Hence, surface ozonation could be a better choice for the pretreatment of medical polymer. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Co-reporter:Jiwei Liu, Yu Zhang, Changzhi Yan, Chunyu Wang, Ruizhi Xu, and Ning Gu
Langmuir 2010 Volume 26(Issue 24) pp:19066-19072
Publication Date(Web):November 19, 2010
DOI:10.1021/la102944h
Highly magnetic luminescent alginate-templated composite microparticles were successfully synthesized by a novel process combining emulsification and layer-by-layer self-assembly techniques. The composite microparticles were characterized by ζ-potential analyzer, transmission electron microscope, X-ray diffraction, Fourier transform infrared spectroscope, fluorescence spectrophotometer, and vibrating sample magnetometer. Experimental observations indicated that the composite microparticles had excellent magnetic properties, and its photoluminescence could be precisely controlled by varying the number of deposition cycles of polyelectrolytes and CdTe/polyelectrolyte multilayers. Moreover, the composite microparticles could be heated up in a high-frequency magnetic field and demonstrated linear temperature-dependent photoluminescence over the range from room temperature to hyperthermia temperature. The composite microparticles are expected to be promising candidates for biomedical applications, such as immunoassay, biosensing and imaging, and cancer diagnosis and treatment.
Co-reporter:Yang Li and Ning Gu
The Journal of Physical Chemistry B 2010 Volume 114(Issue 8) pp:2749-2754
Publication Date(Web):February 10, 2010
DOI:10.1021/jp904550b
The interactions between charged nanoparticles (NPs) and charge-neutral phospholipid membranes are investigated by coarse-grained molecular dynamics simulations. Three kinds of nanoparticles are modeled with different surface charge densities: the uncharged one, the positively charged one, and the negatively charged one. We find that the electrostatic attraction improves the adhesion of a charged nanoparticle to the membrane. With the increase of electrostatic energy, a charged NP can be almost fully wrapped by the membrane. In addition, analyses of structural variations suggest that the adhesion of a charged NP induces a local transition in fluid bilayers. Some thermodynamic quantities such as free energy, entropy, and enthalpy are also obtained to explain the process of NPs binding. Furthermore, the bending energy of wrapping of NPs against the electrostatic potential energy is also discussed based on the Helfrich theory, indicating that the driving force of the wrap originates from the gain in electrostatic energy at the cost of the elastic energy of biomembranes. Our observations shed light on the origin of experiments of the wrap as well as the mechanism of structural transitions of membranes due to the electrostatic binding.
Co-reporter:Xiaoli Jiang, Xuefeng Zhou, Yu Zhang, Tianzhu Zhang, Zhirui Guo and Ning Gu
Langmuir 2010 Volume 26(Issue 4) pp:2477-2483
Publication Date(Web):September 23, 2009
DOI:10.1021/la9027139
In the present study, we introduced Ag nanoparticles into polymer and found for the first time that Ag nanoparticles can induce the formation of breath figure (BF) arrays on polymer surfaces. The effect of Ag nanoparticles has a balance with the BF process, which is influenced by humidity levels and polymers. These nanoparticle-induced BF process involves an interesting interaction between two self-assembly processes on different length scales. The aggregation of Ag nanoparticles on the water/polymer interface might be the key to their inducing ability. Hence, the interfacial-active Ag nanoparticles can be utilized to widen the applications of the BF method and to fabricate a wide variety of novel functionalized porous polymer films.
Co-reporter:Weixin Zhang;Jianfei Sun Dr.;Tingting Bai;Chunyu Wang;Kehu Zhuang;Yu Zhang Dr. Dr.
ChemPhysChem 2010 Volume 11( Issue 9) pp:1867-1870
Publication Date(Web):
DOI:10.1002/cphc.201000056
Co-reporter:Xiaoqing Hua, Tianzhu Zhang, Jing Ren, Zhigang Zhang, Zhenling Ji, Xiaoli Jiang, Jingjing Ling, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2010 Volume 369(1–3) pp:128-135
Publication Date(Web):20 October 2010
DOI:10.1016/j.colsurfa.2010.08.009
Modification of polypropylene (PP) surface with poly(l-lactic acid) (PLLA) via a facile approach was described. The PP flakes were first treated with O2 plasma and then grafted with l-lactic acid (LLA) monomer in the aqueous solution. The attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) were employed to probe the surface composition and morphology of the flakes. Water contact angle measurements were used to monitor the change in hydrophilicity of PP flake surface, and tensile strength tests were carried out to monitor the mechanical properties of PP flakes along the treatment procedure. It was found that the PLLA grafting degree increases reasonably with the reaction temperature. At the same time, a grafting polymerization of 6 h of l-lactic acid at 160 °C can lead to obvious IR absorption. PLLA-grafted polypropylene (PP-g-PLLA) was eventually obtained. The higher reaction temperature can bring the detrimental influences to the mechanical properties of PP flakes.
Co-reporter:Jiwei Liu, Yu Zhang, Chunyu Wang, Ruizhi Xu, Zhongping Chen and Ning Gu
The Journal of Physical Chemistry C 2010 Volume 114(Issue 17) pp:7673-7679
Publication Date(Web):April 14, 2010
DOI:10.1021/jp911933b
Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules were successfully synthesized by a novel process combining emulsification and layer-by-layer self-assembly techniques. The as-synthesized microcapsules (2.67 μm in diameter) were superparamagnetic with a saturation magnetization of 14.2 emu·g−1, which contained approximately 30 wt % maghemite nanoparticles. The drug (doxorubicin) encapsulation efficiency was 56.4% and loading content was 3.5%. The in vitro release behavior under a high-frequency magnetic field (HFMF) indicated that the applied HFMF accelerated significantly the drug release from the microcapsules, which might be related to the microcapsules’ magnetic properties. Moreover, the in vitro cytotoxicity of doxorubicin-loaded alginate-templated polyelectrolyte multilayer microcapsules and the doxorubicin released from the microcapsules were investigated.
Co-reporter:Jianfei Sun, Feng Sun, Beibei Xu, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2010 360(1–3) pp: 94-98
Publication Date(Web):
DOI:10.1016/j.colsurfa.2010.02.012
Co-reporter:Kang Xu, Zhi rui Guo, Ning Gu
Chinese Chemical Letters 2009 Volume 20(Issue 2) pp:241-244
Publication Date(Web):February 2009
DOI:10.1016/j.cclet.2008.10.053
We herein report a one-step, wet-chemical approach to synthesizing gold nanoplates in large quantities via the AuCl4− thermal reduction process by aniline, without introducing additional capping agent or surfactant. It is found that the reduction kinetics of AuCl4− is greatly altered by varying the initial molar ratio of aniline to AuCl4−. Moreover, further investigation reveals that the in-situ formed polyaniline could serve effectively as a capping agent to preferably adsorb the {1 1 1} facets of gold crystals during a slow reduction process, directing the formation of gold nanoplates.
Co-reporter:Ji Wei Liu, Yu Zhang, Cun Wang Ge, Yong Long Jin, Sun Ling Hu, Ning Gu
Chinese Chemical Letters 2009 Volume 20(Issue 8) pp:977-980
Publication Date(Web):August 2009
DOI:10.1016/j.cclet.2009.03.036
Highly luminescent water-soluble CdTe quantum dots (QDs) have been synthesized with an electrogenerated precursor. The obtained CdTe QDs can possess good crystallizability, high quantum yield (QY) and favorable stability. Furthermore, a detection system is designed firstly for the investigation of the temperature-dependent PL of the QDs.
Co-reporter:Fang Yang;YiXin Li;ZhongPing Chen
Science Bulletin 2009 Volume 54( Issue 17) pp:2934-2939
Publication Date(Web):2009 September
DOI:10.1007/s11434-009-0168-5
Encapsulated gas microbubbles are well known as ultrasound contrast agents (UCAs) for medical ultrasound (US) imaging. With the development of shell materials and preparation technologies, the application of microbubbles has been enormously popular in molecular imaging, drug delivery and targeted therapy, etc. The objective of this study is to develop Fe3O4 nanoparticle-inclusion microbubble construct. The in vitro US imaging experiment indicates that the Fe3O4 nanoparticle-inclusion microbubbles have higher US enhancement than those without Fe3O4 nanoparticle-inclusion. According to the microbubble dynamic theory, the acoustic scattering properties can be quantified by scattering cross-section of the shell. The scattering study on Fe3O4 nanoparticle-inclusion microbubbles of different concentration shows that within a certain range of concentration, the scattering cross-section of microbubble increases with the addition of Fe3O4 nanoparticles. When exceeding the concentration range, the ultrasonic characteristic of microbubbles is damped. On the other hand, since Fe3O4 nanoparticles can also serve as the Magnetic Resonance Imaging (MRI) contrast agent, they can be potentially used as contrast agents for the double-modality (MRI and US) clinical studies. However, it is important to control the concentration of Fe3O4 nanoparticles in the shell in order to realize the combined functions of US and MRI.
Co-reporter:ZP Chen;RZ Xu;Y Zhang;N Gu
Nanoscale Research Letters 2009 Volume 4( Issue 3) pp:
Publication Date(Web):2009 March
DOI:10.1007/s11671-008-9226-1
Monodisperse magnetic nanoparticles (MNPs) were synthesized by thermal decomposition of iron-oleate and functionalized with silanes bearing various functional groups such as amino group (NH2), short-chain poly(ethylene glycol) (PEG), and carboxylic group (COOH). Then, silanes-functionalized magnetic nanoparticles (silanes-MNPs) were incubated in cell culture medium plus fetal calf serum to investigate the effects of proteins from culture medium on surface property of MNPs. Zeta potential measurements showed that although surface charges of silanes-MNPs were different, they exhibited negative charges at neutral pH and approximate isoelectric points after they were incubated in cell culture medium. The reason was that silanes-MNPs could easily adsorb proteins from culture medium via non-covalent binding, resulting in the formation of protein-silanes-MNPs conjugates. Moreover, silanes-MNPs with various functional groups had different adsorption capacity to proteins, as confirmed by Coomassie blue fast staining method. The in vitro cell experiments showed that protein-silanes-MNPs had higher cellular uptake by cancer cells than silanes-MNPs.
Co-reporter:Yuqing Ge;Yu Zhang;Shiying He;Fang Nie;Gaojun Teng
Nanoscale Research Letters 2009 Volume 4( Issue 4) pp:
Publication Date(Web):2009 April
DOI:10.1007/s11671-008-9239-9
Labeling of cells with nanoparticles for living detection is of interest to various biomedical applications. In this study, novel fluorescent/magnetic nanoparticles were prepared and used in high-efficient cellular imaging. The nanoparticles coated with the modified chitosan possessed a magnetic oxide core and a covalently attached fluorescent dye. We evaluated the feasibility and efficiency in labeling cancer cells (SMMC-7721) with the nanoparticles. The nanoparticles exhibited a high affinity to cells, which was demonstrated by flow cytometry and magnetic resonance imaging. The results showed that cell-labeling efficiency of the nanoparticles was dependent on the incubation time and nanoparticles’ concentration. The minimum detected number of labeled cells was around 104by using a clinical 1.5-T MRI imager. Fluorescence and transmission electron microscopy instruments were used to monitor the localization patterns of the magnetic nanoparticles in cells. These new magneto-fluorescent nanoagents have demonstrated the potential for future medical use.
Co-reporter:Song Zhang;Xiangjian Chen;Chunrong Gu;Yu Zhang;Jindan Xu
Nanoscale Research Letters 2009 Volume 4( Issue 1) pp:
Publication Date(Web):2009 January
DOI:10.1007/s11671-008-9204-7
Recently, magnetic nanoparticles of iron oxide (Fe3O4, γ-Fe2O3) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe2O3is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies.
Co-reporter:J.W. Liu, Y. Zhang, D. Chen, T. Yang, Z.P. Chen, S.Y. Pan, N. Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2009 Volume 341(1–3) pp:33-39
Publication Date(Web):5 June 2009
DOI:10.1016/j.colsurfa.2009.03.033
A novel process combining emulsification with sol–gel method is described to synthesize γ-Fe2O3/alginate/silica microspheres. The synthesis procedure consists of two steps: (1) synthesis of magnetic alginate microspheres via an emulsification technique; (2) in situ synthesis of magnetic silica microspheres by the hydrolysis of TEOS in the presence of ammonia solution. The as-synthesized composite microspheres with a typical average diameter of 4.4 μm were spherical and superparamagnetic. Moreover, they contained up to 31.7 wt% maghemite with a saturation magnetization of 15.1 emu g−1. The application of these magnetic microspheres as adsorbents for isolation of plasma DNA has also been studied.
Co-reporter:Yuqing Ge, Yu Zhang, Jingguang Xia, Ming Ma, Shiying He, Fang Nie, Ning Gu
Colloids and Surfaces B: Biointerfaces 2009 Volume 73(Issue 2) pp:294-301
Publication Date(Web):15 October 2009
DOI:10.1016/j.colsurfb.2009.05.031
We synthesized three types of magnetic iron oxide nanoparticles (MNPs), which were meso-2,3-dimercaptosuccinic acid (DMSA) coated MNPs (DMSA@MNPs, 17.3 ± 4.8 nm, negative charge), chitosan (CS) coated MNPs (CS@MNPs, 16.5 ± 6.1 nm, positive charge) and magnetic nanoparticles agglomerates, formed by electronic aggregation between DMSA@MNPs and CS (CS-DMSA@MNPs, 85.7 ± 72.9 nm, positive charge) respectively. The interactions of these MNPs with Oral Squamous Carcinoma Cell KB were investigated. The results showed that cellular uptakes of MNPs were on the dependence of incubation time, nanoparticles concentration and nanoparticles properties such as surface charge, size, etc. The cellular uptake was enhanced with the increase of incubation time and nanoparticles concentration. Although all MNPs could enter to cells, we observed apparent differences in the magnitude of nanoparticles uptaken. The cellular uptake of CS-DMSA@MNPs by KB cells was the highest and that of DMSA@MNPs was the lowest among the three types of MNPs. The same conclusions were drawn via the reduction of water proton relaxation times T2*, resulting from the different iron load of labeled cells using a 1.5 T clinical MR imager. The finding of this study will have implications in the chemical design of nanomaterials for biomedical applications.
Co-reporter:Fang Yang, Ning Gu, Di Chen, Xiaoyu Xi, Dong Zhang, Yixin Li, Junru Wu
Journal of Controlled Release 2008 Volume 131(Issue 3) pp:205-210
Publication Date(Web):12 November 2008
DOI:10.1016/j.jconrel.2008.07.038
Reparable sonoporation of human breast cancer cells was achieved during exposure to moderate ultrasound (spatial peak acoustic pressure, psp = 0.25 MPa, 1 MHz tone-bursts, 20 cycles per tone-burst at pulse repetition frequency of 10 kHz) up to 40 s assisted by the presence of encapsulated microbubbles (EMBs). It was demonstrated that shear stress generated by oscillating EMBs at the cell membranes introduced small transient pores in cell membranes by which cells were able to uptake some extracellular fluid and meanwhile triggered the repairing process through self-sealing during sonoporation. It was also indicated by post-sonoporation analysis using the fluorescent microscopy, scanning electron microscopy, and the Bradford assay which determined the protein content in cell supernatant that the self-sealing might be established by lysosomal-associated membrane protein, LAMP-1, fusing with the plasma membrane under the stressful condition in sonoporation.
Co-reporter:Fang Yang, Aiyuan Gu, Zhongping Chen, Ning Gu, Min Ji
Materials Letters 2008 Volume 62(Issue 1) pp:121-124
Publication Date(Web):15 January 2008
DOI:10.1016/j.matlet.2007.04.111
In order to improve the sensitivity of ultrasound imaging, the contrast agents, a powerful non-invasive and real-time medical imaging technique, are used. However, air or N2 or perfluorocarbon only encapsulated microbubbles which are currently used have lower efficiency and short imaging time. So the novel contrast agents with a higher efficiency are required. To achieve this objective, the strategy that we have explored involves the use of superparamagnetic iron oxide (SPIO) Fe3O4 nanoparticles multilayer emulsion microbubbles. This multilayer structure consists of three layers. The core is poly-d, l-lactide (PLA) encapsulated N2 nanobubble with the SPIO nanoparticles forming oil-in-water (W/O) layer. The outermost is water-in-oil-in-water ((W/O)/W) emulsion layer with PVA solution. Herein we describe the synthesis and characterization of ultrasound imaging microstructure with an overall diameter of around 2μm–8μm. On the one hand, the stable gas encapsulated microstructure can provide a high scattering intensity resulting in high echogenicity, On the other hand, SPIO nanoparticles have shown the potential of high-resolution sonography. So the multiple emulsion microbubbles with SPIO can have double action to enhance the ultrasound imaging. Besides, because SPIO can also serve as magnetic resonance imaging (MRI) contrast agents, such microstructure may be useful for multimodality imaging studies in ultrasound imaging and MRI.
Co-reporter:Fang Fang Peng, Yu Zhang, Ning Gu
Chinese Chemical Letters 2008 Volume 19(Issue 6) pp:730-733
Publication Date(Web):June 2008
DOI:10.1016/j.cclet.2008.03.021
Peroxidase-like catalytic properties of Fe3O4 nanoparticles (NPs) with three different sizes, synthesized by chemical coprecipitation and sol–gel methods, were investigated by UV–vis spectrum analysis. By comparing Fe3O4 NPs with average diameters of 11, 20, and 150 nm, we found that the catalytic activity increases with the reduced nanoparticle size. The electrochemical method to characterize the catalytic activity of Fe3O4 NPs using the response currents of the reaction product and substrate was also developed.
Co-reporter:Zhirui Guo, Yu Zhang, Aiqun Xu, Meng Wang, Lan Huang, Kang Xu and Ning Gu
The Journal of Physical Chemistry C 2008 Volume 112(Issue 33) pp:12638-12645
Publication Date(Web):July 31, 2008
DOI:10.1021/jp8028962
Layered assemblies of single crystal gold nanoplates are directly synthesized in large scale by simply adding aniline to HAuCl4−HCl aqueous solution at room temperature, without the need of extra capping agent or surfactant. In this approach, the large amount of Cl−, the oxidative etching by the O2/Cl− pair, the protonation of aniline, and the mild reaction temperature cocontribute to greatly slow up the reduction process of AuCl4− for facilitating the formation of these anisotropic gold nanostructures. The as-synthesized layered assemblies consist of inseparable gold nanoplates interconnected via steps between layers, which are confirmed by SEM and TEM. Moreover, these layered assemblies are further characterized by EDX, SAED, FT-IR, XRD, and UV−vis−NIR, respectively. The effects of different synthetic parameters on the shape and size of the final gold product are investigated. On the basis of a series of experimental results, it is revealed that in situ produced polyaniline with rigidly straight chain molecular structure plays a key role in achieving these gold layered assemblies. The possible growth mechanism is also proposed.
Co-reporter:Z.P. Chen, Y. Zhang, S. Zhang, J.G. Xia, J.W. Liu, K. Xu, N. Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2008 Volume 316(1–3) pp:210-216
Publication Date(Web):5 March 2008
DOI:10.1016/j.colsurfa.2007.09.017
A simple, but efficient method for preparation of water-soluble iron oxide nanoparticles has been developed. Monodisperse Fe3O4 nanoparticles were synthesized by thermal decomposition of iron-oleate. Surface double-exchange of oleic acid capped monodisperse Fe3O4 nanoparticles with a familiar 2,3-dimercaptosuccinnic acid (HOOC–CH(SH)–CH(SH)–COOH, DMSA) was first performed in chloroform in the presence of triethylamine, and then this process was repeated in ethanol under the same conditions. The resulting Fe3O4 nanoparticles could be transferred into water to form stable magnetic fluid without post-treatment processes such as filtration and re-concentration. TEM images show that water-soluble Fe3O4 nanoparticles remain monodisperse and even form a monolayer of ordered assembly, and the results of TGA, VSM show that Fe3O4 nanoparticles via surface double-exchange possess more DMSA molecules through intermolecular disulfide cross-linking between DMSA, as confirmed by Raman spectra. Zeta potential measurements show that nanoparticles after surface double-exchange are negatively charged in the range of pH = 1–14, and stability assays exhibit their excellent stability in water and other physiological environments.
Co-reporter:Jianfei Sun Dr.;Haoyan Zhou;Yonglong Jin Dr.;Meng Wang Dr.;Yifei Li Dr.
ChemPhysChem 2008 Volume 9( Issue 13) pp:1847-1850
Publication Date(Web):
DOI:10.1002/cphc.200800237
Co-reporter:Yang Li, Xin Chen and Ning Gu
The Journal of Physical Chemistry B 2008 Volume 112(Issue 51) pp:16647-16653
Publication Date(Web):November 25, 2008
DOI:10.1021/jp8051906
Understanding the interactions of nanoparticles (NPs) with biological system, especially interactions with cell membranes, is critical for the rational design of nanocarrier agents and drug delivery systems. Here, we have performed coarse-grained molecular dynamics simulations aimed at the effect of hydrophilic/hydrophobic properties of nanoparticles on the interaction with cell membranes (dipalmitoylphosphatidylcholine or DPPC bilayer). Two kinds of nanoparticles (hydrophobic and semihydrophilic) are modeled in the simulation. The results indicate that a hydrophobic nanoparticle can result in the inclusion into the bilayer, whereas a semihydrophilic nanoparticle is only found to adsorb into the membrane. For different system free energy profiles have been calculated to elucidate those phenomena. For the semihydrophilic nanoparticle case, we also discuss the potential substantial energy barrier of particle wrapping, implicating that the endocytosis-like mechanism is an energy-mediated process. The landscapes of the membrane fluctuation in the transitions imply that the deformation of the lipid bilayer induced by the addition of NPs is short-range, and the rearrangement of lipid molecules plays a significant role for morphological variations of NP-containing lipid membrane patches. These results show that the surface hydrophobicity can result in different response mechanisms of NP−biomembrane interactions.
Co-reporter:Zhirui Guo, Yu Zhang, Lan Huang, Meng Wang, Jing Wang, Jianfei Sun, Lina Xu, Ning Gu
Journal of Colloid and Interface Science 2007 Volume 309(Issue 2) pp:518-523
Publication Date(Web):15 May 2007
DOI:10.1016/j.jcis.2006.12.070
We report a general and versatile method for controlled synthesis of anisotropic gold nanostructures through the reduction of HAuCl4 by aniline in aqueous solution, without the need for an additional stabilizer or capping agent. In this approach, the reduction kinetics of AuCl−4 can be altered by simply adjusting the initial pH and temperature, inducing the formation of a wide variety of anisotropic nanostructures such as dispersed or multilayered plates, wires with networked or paramecium-like structures, and ginger-shaped particles. AFM, TEM, XRD, EDX, FTIR, and UV–vis–NIR measurements were used to characterize the resulting gold nanostructures. Investigation reveals that in situ formed polyaniline serves effectively as a capping agent to direct the shape of gold nanostructures during the slow growth process. These as-synthesized gold nanostructures exhibit strongly shape-dependent optical properties. This facile approach may be extended to the synthesis of some other anisotropic metal nanostructures such as platinum or palladium.In the aniline reduction of HAuCl4, the reduction kinetics of AuCl−4 can be altered by varying the initial pH and temperature, inducing the formation of various anisotropic gold nanostructures.
Co-reporter:Jing Wang, Shiying He, Shengli Xie, Lina Xu, Ning Gu
Materials Letters 2007 Volume 61(Issue 3) pp:917-920
Publication Date(Web):February 2007
DOI:10.1016/j.matlet.2006.06.019
As a powerful method for the study of mechanical properties at micro-/nanoscale, nanoindentation was applied to measure the hardness and elastic modulus of bacteria-templated metallic nanomaterials for the first time. Based on the morphological characterization by Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM), nanoindentation testing results showed that after coating with nickel via electroless chemical plating, the elastic modulus and hardness of bacterial cells were increased about 17 times and 50 times, respectively, indicating a great improvement in mechanical properties. This study would lay a forceful mechanical foundation for a better and general understanding of this kind of biotemplated metallic nanomaterials, which showed potential applications in nanoelectronics, nanomagnetism and nanomechanics.
Co-reporter:Shiying He, Zhirui Guo, Yu Zhang, Song Zhang, Jing Wang, Ning Gu
Materials Letters 2007 Volume 61(Issue 18) pp:3984-3987
Publication Date(Web):July 2007
DOI:10.1016/j.matlet.2007.01.018
The use of microorganisms in the synthesis of nanoparticles emerges as an eco-friendly and exciting approach. In this study, the bacteria Rhodopseudomonas capsulata was screened and found to successfully produce gold nanoparticles of different sizes and shapes. The important parameter, which controls the size and shape of gold nanoparticles, was pH value. The R. capsulata biomass and aqueous HAuCl4 solution were incubated at pH values ranging from 7 to 4. The results demonstrated that spherical gold nanoparticles in the range of 10–20 nm were observed at pH value of 7 whereas a number of nanoplates were observed at pH 4.
Co-reporter:Jing Wang;ShiYing He;LiNa Xu
Science Bulletin 2007 Volume 52( Issue 21) pp:2919-2924
Publication Date(Web):2007 November
DOI:10.1007/s11434-007-0390-y
Recently bacterial cells have become attractive biological templates for the fabrication of metal nanostructures or nanomaterials due to their inherent small size, various standard geometrical shapes and abundant source. In this paper, nickel-coated bacterial cells (gram-negative bacteria of Escherichia coli) were fabricated via electroless chemical plating. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) characterization results reveal evident morphological difference between bacterial cells before and after deposition with nickel. The bare cells with smooth surface presented transverse outspreading effect at mica surface. Great changes took place in surface roughness for those bacterial cells after metallization. A large number of nickel nanoparticles were observed to be equably distributed at bacterial surface after activation and subsequent metallization. Furthermore, ultra thin section analytic results validated the presence and uniformity of thin nickel coating at bacterial surface after metallization.
Co-reporter:Song Zhang, Zhiping Bian, Chunrong Gu, Yu Zhang, Shiying He, Ning Gu, Jinan Zhang
Colloids and Surfaces B: Biointerfaces 2007 Volume 55(Issue 2) pp:143-148
Publication Date(Web):1 April 2007
DOI:10.1016/j.colsurfb.2006.11.041
Maghemite nanoparticles (MNPs) were synthesized by chemical coprecipitation and coated with meso-2,3-dimercaptosuccinic acid (HOOC-CH(SH)-CH(SH)-COOH or DMSA). The morphology and properties of the nanoparticles were characterized by TEM, XRD, Zeta Potential Analyzer and VSM. Subsequentially, the anti-human cardiac troponin I (cTnI) immunomagnetic nanoparticles (IMNPs) were prepared by grafting anti-human cTnI antibodies on the surface of DMSA-coated MNPs using the linker of EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride). The conjugation amount of the antibodies and the activity of IMNPs was evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. The results show that the physical and chemical adsorption occurred at the same time, but the former was unstable and apt to desorb, and the maximum conjugation amount of antibody was about 96 μg on the 0.1 mg MNPs by covalent bond. The stability was also investigated, and after 300 days the antibodies on the IMNPs remained the biological activity.
Co-reporter:Jianfei Sun Dr.;Yu Zhang Dr.;Zhongping Chen Dr.;Jie Zhou Dr. Dr.
Angewandte Chemie 2007 Volume 119(Issue 25) pp:
Publication Date(Web):15 MAY 2007
DOI:10.1002/ange.200604474
Feldabhängig: In einem zeitlich variierten Magnetfeld aggregieren elektrostatisch stabilisierte Magnetit-Nanopartikel zu mikrometergroßen faserförmigen Überstrukturen (siehe Bild), während sterisch stabilisierte Kolloide diese Strukturbildung nicht eingehen. Es wird vermutet, dass das Magnetfeld zwischen der elektrostatischen und der magnetischen Wechselwirkung vermittelt.
Co-reporter:Jianfei Sun Dr.;Yu Zhang Dr.;Zhongping Chen Dr.;Jie Zhou Dr. Dr.
Angewandte Chemie International Edition 2007 Volume 46(Issue 25) pp:
Publication Date(Web):15 MAY 2007
DOI:10.1002/anie.200604474
In the field: In the presence of a time-varied magnetic field, electrostatically stabilized magnetite nanoparticles aggregate into microsized fibrous suprastructures (see image). The process is irreproducible for sterically stabilized colloids. It is inferred that the phenomenon results from the co-effects of magnetic moment interaction and electrostatic interaction that are connected by the time-varied magnetic field.
Co-reporter:Wang Yihong, Wei Song, Zhou Jie, Gu Ning, K.D. Wesche
Applied Surface Science 2006 Volume 252(Issue 23) pp:8264-8269
Publication Date(Web):30 September 2006
DOI:10.1016/j.apsusc.2005.10.053
Abstract
A self-assembled monolayers (SAMs) of (3-mercaptopropy) trimethoxysilane (3-MPT) chemisorbed on silver surface was chemically modified by 1-octadecanethiol (C18H37SH) (to form self-assembled mixed-monolayer (SAMM)) and the co-polymer of N-vinylcarbazole and methyl methacrylate ester to form complex self-assemblied film (CSAF). The combinative state of interface between SAMs (or SAMM) and co-polymer were characterized by dynamic mechanical thermal analysis (DMTA). The thickness of film on Ag was characterized by X-ray photoelectron spectroscopy (XPS). Cyclic voltammetry (CV) measurements in 10% NaOH aqueous solution with the silver surface and covered with film indicated that 3-MPT SAMs modified with C18H37SH and then with co-polymer have higher capability against oxidation.
Co-reporter:Yihong Wang, Wei Song, Cunwang Ge, Ning Gu, K.-D. Wesche
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2006 Volume 287(1–3) pp:226-231
Publication Date(Web):15 September 2006
DOI:10.1016/j.colsurfa.2006.05.043
The saturated adsorption of the (3-mercaptopropyl)trimethoxysilane (SHC3H6Si(OCH3)3, 3-MPT) self-asemblied monolayers (SAMs) on silver powder was firstly determined. A quantitative analysis of 3-MPT suggests that there is a lower saturation adsorption than that of 1-octadecanethiol (C18H37SH) on Ag at room temperature. The exchange reaction of C18H37SH replacing 3-MPT at different temperatures indicates that a great quantity of 3-MPT on the surface remains unexchangable. The study on co-adsorption reaction of two thiols shows that only 3-MPT adsorption is diffusion-controlling course at the early stage at lower temperature, while others display a thermodynamical controlling process. The ratio of C18H37SH to 3-MPT (C18H37SH/SHC3H6Si(OCH3)3) at co-adsorption equilibrium on surface is around 2.3 in the experimental temperature range. Contact angle measurements support the above results and show that the self-assemblied mixed monolayer (SAMM) formed by two thiols was better order in higher temperature.
Co-reporter:Zhirui Guo, Yu Zhang, Yun DuanMu, Lina Xu, Shengli Xie, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2006 Volume 278(1–3) pp:33-38
Publication Date(Web):20 April 2006
DOI:10.1016/j.colsurfa.2005.11.075
Micrometer-sized edge, polygonal gold plates of several 10 nm thickness, called gold nanoplates, have been synthesized in large quantities through simply introducing aniline to a heated ethylene glycol (EG) solution of hydrogen tetrachloroaurate (HAuCl4·4H2O) without any other capping agents or surfactants. Electron diffraction (ED) and X-ray diffraction (XRD) patterns identified the as-prepared gold nanoplates were single crystals bound primarily by {1 1 1} facets. The study of the optical properties showed these large gold nanoplates had strong absorption in near infrared region (NIR). Investigations suggested the amount of aniline added to the reaction solution played a key role in producing gold nanoplates and the size of the gold nanoplates can be tuned by adjusting the stirring speed. The possible formation mechanism of the as-prepared gold nanoplates was also discussed.
Co-reporter:Jianhui Liao, Yu Zhang, Wei Yu, Lina Xu, Cunwang Ge, Jinhong Liu, Ning Gu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2003 Volume 223(1–3) pp:177-183
Publication Date(Web):21 August 2003
DOI:10.1016/S0927-7757(03)00156-0
Gold colloidal particles were found to spontaneously organize into linear aggregates in ethanol. The morphology of these aggregates was characterized with transmission electron microscope (TEM) and atomic force microscope (AFM), which revealed the quasi one-dimensional (1D) chain-like shape. Immobilization of these chains from solution onto substrate surface as well as the measurement of UV–visible extinction spectrum was performed to investigate the aggregation mechanism. The results presented the evidence for the existence of the nanoparticle chains in solution. Moreover, the kinetic aspects of the chain-like aggregation were detailed studied using UV–visible spectroscopy. It is believed that dipole–dipole interaction is the driving force of nanoparticle linear aggregation. This finding provides a novel strategy for the construction of quasi 1D structures, which are suitable for the fabrication of solid-state devices based on single-electron tunneling.
Co-reporter:Hao Wu, Jun Lin, Peidang Liu, Zhihai Huang, Peng Zhao, Haizhen Jin, Jun Ma, Longping Wen, Ning Gu
Biomaterials (September 2016) Volume 101() pp:1-9
Publication Date(Web):September 2016
DOI:10.1016/j.biomaterials.2016.05.031
Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy.
Co-reporter:Hao Wu, Jun Lin, Peidang Liu, Zhihai Huang, Peng Zhao, Haizhen Jin, Jun Ma, Longping Wen, Ning Gu
Biomaterials (September 2016) Volume 101() pp:1-9
Publication Date(Web):September 2016
DOI:10.1016/j.biomaterials.2016.05.031
Co-reporter:Fei Xiong, Caiyun Yan, Jilai Tian, Kunkun Geng, ... Ning Gu
Journal of Pharmaceutical Sciences (December 2014) Volume 103(Issue 12) pp:4030-4037
Publication Date(Web):1 December 2014
DOI:10.1002/jps.24209
Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2O3@DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2O3@DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2O3@DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2O3@DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2O3@DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex®. Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2O3@DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2O3@DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Co-reporter:Qi Ding, Dongfang Liu, Dawei Guo, Fang Yang, Xingyun Pang, Renchao Che, Naizhen Zhou, Jun Xie, Jianfei Sun, Zhihai Huang, Ning Gu
Biomaterials (April 2017) Volume 124() pp:
Publication Date(Web):April 2017
DOI:10.1016/j.biomaterials.2017.01.043
Superparamagnetic Fe3O4 nanoparticles (NPs)-based hyperthermia is a promising non-invasive approach for cancer therapy. However, the heat transfer efficiency of Fe3O4 NPs is relative low, which hinders their practical clinical applications. Therefore, it is promising to improve the magnetic hyperthermia efficiency by exploring the higher performance magnetic NPs-based hybrid nanostructures. In the current study, it presents a straightforward in situ reduction method for the shape-controlled preparation of magnetite (Fe3O4) silver (Ag) hybrid NPs designed as magnetic hyperthermia heat mediators. The magnetite silver hybrid NPs with core-shell (Fe3O4@Ag) or heteromer (Fe3O4-Ag) structures exhibited a higher biocompatibility with SMMC-7721 cells and L02 cells than the individual Ag NPs. Importantly, in the magnetic hyperthermia, with the exposure to alternating current magnetic field, the Fe3O4@Ag and Fe3O4-Ag hybrid NPs indicated much better tumor suppression effect against SMMC-7721 cells than the individual Fe3O4 NPs in vitro and in vivo. These results demonstrate that the hybridisation of Fe3O4 and Ag NPs could greatly enhance the magnetic hyperthermia efficiency of Fe3O4 NPs. Therefore, the Fe3O4@Ag and Fe3O4-Ag hybrid NPs can be used to be as high performance magnetic hyperthermia mediators based on a simple and effective preparation approach.
Co-reporter:Peidang Liu, Ling Chen, Xiuying Bai, Andrew Karaplis, Dengshun Miao, Ning Gu
Brain Research (15 September 2011) Volume 1412() pp:9-17
Publication Date(Web):15 September 2011
DOI:10.1016/j.brainres.2011.07.028
Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. Effects of FGF-23 on skeleton, phosphate homeostasis, and cardiovascular system have been investigated; however, the effect of FGF-23 on the central nervous system (CNS) is unknown. To assess whether FGF-23 influences the function and structure of the CNS and whether the effect of FGF-23 on the CNS is mediated by FGF receptors directly or by hypophosphatemia indirectly, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet containing a normal diet plus 1.25% phosphate in drinking water from weaning for 5 weeks and the phenotypes of the CNS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet showed impaired spatial learning and memory. Furthermore, these mice exhibited the impairment of long-term potentiation in hippocampal CA1 region, and the reduction of hippocampal adenosine-triphosphate content and of choline acetyltransferase-positive neurons in basal forebrain, possibly as pathogenetic factors contributing to the cognitive deficit. The central nervous phenotypes of transgenic mice were rescued following improved hypophosphatemia by the high-phosphate diet intake. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CNS mediated by the secondary severe hypophosphatemia.► FGF-23 overexpression resulted in cognitive dysfunction. ► FGF-23 overexpression resulted in impairment of LTP in hippocampal CA1 region. ► FGF-23 overexpression resulted in reduction of hippocampal ATP content and of ChAT-positive neurons in basal forebrain. ► The central nervous phenotypes were rescued following improved hypophosphatemia. ► The effect of FGF-23 overexpression on the CNS is mediated by the secondary severe hypophosphatemia.
Co-reporter:Wei Zhang, Ying Sun, Zhichao Lou, Lina Song, Yang Wu, Ning Gu, Yu Zhang
Colloids and Surfaces B: Biointerfaces (1 March 2017) Volume 151() pp:
Publication Date(Web):1 March 2017
DOI:10.1016/j.colsurfb.2016.12.025
•Hemin was immobilized on PEG-GO sheets successfully.•PEG-GO-Hemin has higher peroxidase-like activity than hemin or GO alone.•PEG-GO-Hemin could induce cytotoxicity via the oxidation of LDL.•GO has potential hazard under oxidative stress conditions.In this study, PEGylated graphene oxide (PEG-GO)-hemin composite structure was constructed. Hemin in the form of nanoscaled aggregates were immobilized on PEG-GO sheets by the π-π stacking super-molecular interaction. Via catalyzing the oxidation of chromogenic substrates, we elicited the obtained PEG-GO-Hemin composite sheets have much higher peroxidase-like activity compared to hemin or PEG-GO alone, which is due to the introduction of enzyme active center of hemin with high dispersity, the excellent affinity to organic substrate through π-π stacking and/or electrostatic adsorption and the rapid electron transfer capability of PEG-GO. Similarly, PEG-GO-Hemin was found to be able to catalyze the oxidation of low density lipoprotein (LDL) by H2O2, resulting in toxicity to porcine iliac endothelial cells (PIECs) in vitro. Furthermore, we also demonstrated that PEG-GO sheets showed enhanced peroxidase activity when met hemin containing proteins including hemoglobin and cytochrome c. High glucose level (HG) in human umbilical vein endothelial cells (HUVECs) can induce cytochrome c to release from the respiratory chain, thus applying PEG-GO under HG condition could cause a much higher peroxidase-like activity, resulting in the production of hydroxyl radical (OH) and cytochrome c radical (cytochrome c), which eventually enhance the apoptosis. These results suggest GO has potential hazard for biomedical applications in some pathophysiological conditions.
Co-reporter:Jin-Long Chen, Li Li, Shuo Wang, Xiao-Yan Sun, Lu Xiao, Jia-Shu Ren, Bin Di and Ning Gu
Journal of Materials Chemistry A 2017 - vol. 5(Issue 27) pp:NaN5344-5344
Publication Date(Web):2017/06/07
DOI:10.1039/C7TB00864C
Daily monitoring of blood glucose is of great importance for the treatment of diabetes mellitus. Herein, we present an ensemble glucometer with a sandwich structure formed by the spontaneous entrapment of glucose oxidase (GOD) onto manganese dioxide nanosheets (MnO2 NSs) via the hydrophobic effect and hydrogen bond interaction. Within the hybrid glucometer, the ultrathin MnO2 NSs act as an enzyme nanosupport and target-activated signal transducer. Trimodal self-indication by fluorescence (FL) and UV-absorbance (UV) and magnetic resonance signal (MRS) activation with glucose-specificity provides multiple response signals to glucose. Taking account of its operational simplicity and convenience, even being observable by the naked eye, a detection limit as low as 0.1 µM was obtained by using the ensemble glucometer in a colorimetric assay, whilst the precision for 11 replicated detections of 10 µM glucose was 3.5% (relative standard deviation, RSD). Notably, the value of the Michaelis–Menton constant of GOD involved the presented glucometer is estimated to be 0.051 mM, showing an exceptional enhanced enzymatic activity of free GOD measured by far. The designed glucometer, with its high sensitivity and simplicity highlighted, was capable of routine blood glucose monitoring for type-I diabetes mellitus in rats. Furthermore, the fully integrated platform can be readily generalized in principle for a number of biomarkers for point of care diagnostics in the future.
![4-[[4-[[4-(PENTOXYCARBONYLAMINO)CYCLOHEXYL]METHYL]CYCLOHEXYL]CARBAMOYLOXY]BUTYL N-[4-[[4-(BUTOXYCARBONYLAMINO)CYCLOHEXYL]METHYL]CYCLOHEXYL]CARBAMATE](http://img.cochemist.com/ccimg/76700/76600-67-4.png)
![4-[[4-[[4-(PENTOXYCARBONYLAMINO)CYCLOHEXYL]METHYL]CYCLOHEXYL]CARBAMOYLOXY]BUTYL N-[4-[[4-(BUTOXYCARBONYLAMINO)CYCLOHEXYL]METHYL]CYCLOHEXYL]CARBAMATE](http://img.cochemist.com/ccimg/76700/76600-67-4_b.png)
![Dimethyl Pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate](http://img.cochemist.com/ccimg/69000/68950-07-2.png)
![Dimethyl Pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate](http://img.cochemist.com/ccimg/69000/68950-07-2_b.png)
![PYRROLO[1,2-A]QUINOLINE-2,3-DICARBOXYLIC ACID, DIMETHYL ESTER](http://img.cochemist.com/ccimg/69000/68950-03-8.png)
![PYRROLO[1,2-A]QUINOLINE-2,3-DICARBOXYLIC ACID, DIMETHYL ESTER](http://img.cochemist.com/ccimg/69000/68950-03-8_b.png)
![6A-[(2-aminoethyl)amino]-6A-deoxy- beta-Cyclodextrin](http://img.cochemist.com/ccimg/61000/60984-63-6.png)
![6A-[(2-aminoethyl)amino]-6A-deoxy- beta-Cyclodextrin](http://img.cochemist.com/ccimg/61000/60984-63-6_b.png)
![5,7-dihydroxy-2-(4-hydroxyphenyl)-6-[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-8-[(2s,3r,4s,5s)-3,4,5-trihydroxyoxan-2-yl]chromen-4-one](http://img.cochemist.com/ccimg/52000/51938-32-0.png)
![5,7-dihydroxy-2-(4-hydroxyphenyl)-6-[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-8-[(2s,3r,4s,5s)-3,4,5-trihydroxyoxan-2-yl]chromen-4-one](http://img.cochemist.com/ccimg/52000/51938-32-0_b.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4_b.png)
![Poly[oxy[(1S)-1-methyl-2-oxo-1,2-ethanediyl]]](http://img.cochemist.com/ccimg/26200/26161-42-2.png)
![Poly[oxy[(1S)-1-methyl-2-oxo-1,2-ethanediyl]]](http://img.cochemist.com/ccimg/26200/26161-42-2_b.png)
![3,5,9-Trioxa-4-phosphapentacosan-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-, inner salt, 4-oxide](http://img.cochemist.com/ccimg/2700/2644-64-6.png)
![3,5,9-Trioxa-4-phosphapentacosan-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-, inner salt, 4-oxide](http://img.cochemist.com/ccimg/2700/2644-64-6_b.png)
