Co-reporter:Nan Chen, Jiang Li, Haiyun Song, Jie Chao, Qing Huang, and Chunhai Fan
Accounts of Chemical Research 2014 Volume 47(Issue 6) pp:1720-1730
Publication Date(Web):March 3, 2014
DOI:10.1021/ar400324n
DNA and DNA structures can also form hybrids with inorganic NMs. Notably, DNA anchored at the interface of inorganic NMs behaves differently from that at the macroscopic interface. Several types of DNA–NM conjugates have exerted beneficial effects for bioassays and in vitro translation of proteins. Even more interestingly, hybrid nanoconjugates demonstrate distinct properties under the context of biological systems such as cultured cells or animal models. These unprecedented properties not only arouse great interest in studying such interfaces but also open new opportunities for numerous applications in artificial and living systems.
Co-reporter:Ying Zhu;Thomas Earnest;Xiaoqing Cai;Zhili Wang;Ziyu Wu;Chunhai Fan
Advanced Materials 2014 Volume 26( Issue 46) pp:7889-7895
Publication Date(Web):
DOI:10.1002/adma.201304281
It is one of the ultimate goals in cell biology to understand the complex spatio–temporal interplay of biomolecules in the cellular context. To this end, there have been great efforts on the development of various probes to detect and localize specific biomolecules in cells with a variety of microscopic imaging techniques. In this Research News, we first summarize several types of microscopy for visualizing specific biomolecular targets. Then we focus on recent advances in the design of X-ray sensitive nanoprobes for applications in synchrotron-based cellular imaging. With the availability of advanced synchrotron techniques, there has been rapid progress toward high-resolution and multi-color X-ray imaging in cells with various types of functional nanoprobes.
Co-reporter:Xiaoming Li;Nan Chen;Yuanyuan Su;Yao He;Min Yin;Min Wei;Lianhui Wang;Wei Huang;Chunhai Fan
Advanced Healthcare Materials 2014 Volume 3( Issue 3) pp:354-359
Publication Date(Web):
DOI:10.1002/adhm.201300294
Co-reporter:Meihua Lin, Yanli Wen, Lanying Li, Hao Pei, Gang Liu, Haiyun Song, Xiaolei Zuo, Chunhai Fan, and Qing Huang
Analytical Chemistry 2014 Volume 86(Issue 5) pp:2285
Publication Date(Web):February 14, 2014
DOI:10.1021/ac500251t
Because of the short size and low abundance of microRNAs, it is challenging to develop fast, inexpensive, and simple biosensors to detect them. In this work, we have demonstrated a new generation (the third generation) of E-DNA sensor for the sensitive and specific detection of microRNAs. Our third generation of E-DNA sensor can sensitively detect microRNA target (microRNA-141) as low as 1 fM. The excellent specificity has been demonstrated by its differential ability to the highly similar microRNA analogues. In our design, the use of DNA tetrahedron ensures the stem-loop structure in well controlled density with improved reactivity. The regulation of the thermodynamic stability of the stem-loop structure decreases the background signal and increases the specificity as well. The enzymes attached bring the electrocatalytic signal to amplify the detection. The combination of these effects improves the sensitivity of the E-DNA sensor and makes it suitable to the microRNA detection. Finally, our third generation of E-DNA sensor is generalizable to the detection of other micro RNA targets (for example, microRNA-21).
Co-reporter:Xiafeng Yang, Jiang Li, Hao Pei, Yun Zhao, Xiaolei Zuo, Chunhai Fan, and Qing Huang
Analytical Chemistry 2014 Volume 86(Issue 6) pp:3227
Publication Date(Web):February 24, 2014
DOI:10.1021/ac500381e
The direct analysis of cancerous cells provides a new way for cancer detection that obviates cell lysis and other tedious steps (e.g., enrichment, purification, and amplification steps). However, the analysis of different cell types remains challenging due to the subtle differences in cell surface features. Here, we have demonstrated nanoplasmonic differentiation of cell types by using DNA–gold nanoparticle nanoconjugates (DNA-AuNPs). Our strategy relies on cross reactive receptors (a collection of DNA-AuNPs) that are employed to bind the different cells that produce fingerprint-like patterns for each type of cell. Because of the enhanced nanoplasmonic effect of AuNPs via seeded-growth, we could effectively differentiate various cell lines, e.g., 786-O, L929, Hela, and RAW264.7, with dark-field microscopy or even naked eyes.
Co-reporter:Huan Zhang, Sisi Jia, Min Lv, Jiye Shi, Xiaolei Zuo, Shao Su, Lianhui Wang, Wei Huang, Chunhai Fan, and Qing Huang
Analytical Chemistry 2014 Volume 86(Issue 8) pp:4047
Publication Date(Web):March 18, 2014
DOI:10.1021/ac500627r
Graphene oxide (GO) is widely used in biosensors and bioimaging because of its high quenching efficiency, facile chemical conjugation, unique amphiphile property, and low cost for preparation. However, the nanometer size effect of GO on GO–DNA interaction has long been ignored and remains unknown. Here we examined the nanometer size effect of GO on GO–DNA interactions. We concluded that GO of ∼200 nm (lateral nanometer size) possessed the highest fluorescence quenching efficiency whereas GO of ∼40 nm demonstrated much weaker ability to quench the fluorescence. We employed the nanometer size effect of GO to program the dynamic ranges and sensitivity of mercury sensors. Three dynamic ranges (1 to 40 nM, 1 to 15 nM, and 0.1 to 5 nM) were obtained with this size modulation. The sensitivity (slope of titration curve) was programmed from 15.3 ± 1.27 nM–1 to 106.2 ± 3.96 nM–1.
Co-reporter:Jiaoyun Xia, Meihua Lin, Xiaolei Zuo, Shao Su, Lianhui Wang, Wei Huang, Chunhai Fan, and Qing Huang
Analytical Chemistry 2014 Volume 86(Issue 14) pp:7084
Publication Date(Web):June 16, 2014
DOI:10.1021/ac5015436
Contamination of heavy metal ions in an aquatic environment poses a serious threat to human health. More seriously, heavy metal ions are usually present in the environment in a mixture, and the synergetic toxicity of multiple heavy metal ions is revealed (Aragay et al. Chem. Rev. 2011, 111, 3433; Chu et al. Aquat. Toxicol. 2002, 61, 53). Unfortunately, most of the existing methods based on DNA sequences are focusing on the detection of one type of metal ions. Simple and multiplexed detection of multiple metal ions has been poorly investigated and remains challenging. Here, we re-engineered the DNA sequences for Pb2+, Hg2+, and Ag+, through which the binding of multiple metal ions initiated the self-assembly of these DNA sequences. On the basis of our rationally designed multicolor fluorescent labeling of the DNA sequences, cascade fluorescence resonance energy transfer (FRET) occurred. As a result, a fingerprint fluorescent spectrum was produced to indicate the presence of a single type of metal ions or multiple metal ions. The major advantages of our cascade FRET fingerprint technology include the following: (1) the “mix and read” detection mode in homogeneous solution is simple without the need of complicated instruments; (2) only single excitation is required to provide the cascade FRET fingerprint spectrum; (3) multiplexed detection capability can be realized intuitively and sensitively.
Co-reporter:Le Liang;Dr. Jiang Li;Dr. Qian Li; Qing Huang;Dr. Jiye Shi; Hao Yan; Chunhai Fan
Angewandte Chemie 2014 Volume 126( Issue 30) pp:7879-7884
Publication Date(Web):
DOI:10.1002/ange.201403236
Abstract
DNA is typically impermeable to the plasma membrane due to its polyanionic nature. Interestingly, several different DNA nanostructures can be readily taken up by cells in the absence of transfection agents, which suggests new opportunities for constructing intelligent cargo delivery systems from these biocompatible, nonviral DNA nanocarriers. However, the underlying mechanism of entry of the DNA nanostructures into the cells remains unknown. Herein, we investigated the endocytotic internalization and subsequent transport of tetrahedral DNA nanostructures (TDNs) by mammalian cells through single-particle tracking. We found that the TDNs were rapidly internalized by a caveolin-dependent pathway. After endocytosis, the TDNs were transported to the lysosomes in a highly ordered, microtubule-dependent manner. Although the TDNs retained their structural integrity within cells over long time periods, their localization in the lysosomes precludes their use as effective delivery agents. To modulate the cellular fate of the TDNs, we functionalized them with nuclear localization signals that directed their escape from the lysosomes and entry into the cellular nuclei. This study improves our understanding of the entry into cells and transport pathways of DNA nanostructures, and the results can be used as a basis for designing DNA-nanostructure-based drug delivery nanocarriers for targeted therapy.
Co-reporter:Le Liang;Dr. Jiang Li;Dr. Qian Li; Qing Huang;Dr. Jiye Shi; Hao Yan; Chunhai Fan
Angewandte Chemie International Edition 2014 Volume 53( Issue 30) pp:7745-7750
Publication Date(Web):
DOI:10.1002/anie.201403236
Abstract
DNA is typically impermeable to the plasma membrane due to its polyanionic nature. Interestingly, several different DNA nanostructures can be readily taken up by cells in the absence of transfection agents, which suggests new opportunities for constructing intelligent cargo delivery systems from these biocompatible, nonviral DNA nanocarriers. However, the underlying mechanism of entry of the DNA nanostructures into the cells remains unknown. Herein, we investigated the endocytotic internalization and subsequent transport of tetrahedral DNA nanostructures (TDNs) by mammalian cells through single-particle tracking. We found that the TDNs were rapidly internalized by a caveolin-dependent pathway. After endocytosis, the TDNs were transported to the lysosomes in a highly ordered, microtubule-dependent manner. Although the TDNs retained their structural integrity within cells over long time periods, their localization in the lysosomes precludes their use as effective delivery agents. To modulate the cellular fate of the TDNs, we functionalized them with nuclear localization signals that directed their escape from the lysosomes and entry into the cellular nuclei. This study improves our understanding of the entry into cells and transport pathways of DNA nanostructures, and the results can be used as a basis for designing DNA-nanostructure-based drug delivery nanocarriers for targeted therapy.
Co-reporter:Le Liang;Dr. Jiang Li;Dr. Qian Li; Qing Huang;Dr. Jiye Shi; Hao Yan; Chunhai Fan
Angewandte Chemie International Edition 2014 Volume 53( Issue 30) pp:
Publication Date(Web):
DOI:10.1002/anie.201405099
Co-reporter:Le Liang;Dr. Jiang Li;Dr. Qian Li; Qing Huang;Dr. Jiye Shi; Hao Yan; Chunhai Fan
Angewandte Chemie 2014 Volume 126( Issue 30) pp:
Publication Date(Web):
DOI:10.1002/ange.201405099
Co-reporter:Bo Li, Jianzhong Yang, Qing Huang, Yi Zhang, Cheng Peng, Yujie Zhang, Yao He, Jiye Shi, Wenxin Li, Jun Hu and Chunhai Fan
NPG Asia Materials 2013 5(4) pp:e44
Publication Date(Web):2013-04-01
DOI:10.1038/am.2013.7
Graphene and its derivatives (for example, nanoscale graphene oxide (NGO)) have emerged as extremely attractive nanomaterials for a wide range of applications, including diagnostics and therapeutics. In this work, we present a systematic study on the in vivo distribution and pulmonary toxicity of NGO for up to 3 months after exposure. Radioisotope tracing and morphological observation demonstrated that intratracheally instilled NGO was mainly retained in the lung. NGO could result in acute lung injury (ALI) and chronic pulmonary fibrosis. Such NGO-induced ALI was related to oxidative stress and could effectively be relieved with dexamethasone treatment. In addition, we found that the biodistribution of 125I-NGO varied greatly from that of 125I ions, hence it is possible that nanoparticulates could deliver radioactive isotopes deep into the lung, which might settle in numerous ‘hot spots’ that could result in mutations and cancers, raising environmental concerns about the large-scale production of graphene oxide.
Co-reporter:Huan Zhang, Cheng Peng, Jianzhong Yang, Min Lv, Rui Liu, Dannong He, Chunhai Fan, and Qing Huang
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 5) pp:1761
Publication Date(Web):February 13, 2013
DOI:10.1021/am303005j
Graphene oxide (GO) is an increasingly important nanomaterial, which exhibits great promise in the area of bionanotechnology and nanobiomedicine. In this study, we synthesized uniform ultrasmall graphene oxide nanosheets with high yield by a convenient way of modified Hummers’ method. The uniform ultrasmall GO nanosheets, which exhibit fluorescence property and outstanding stability in a wide range of pH values, were less than 50 nm. Furthermore, because of the advantages of its lateral size, the uniform ultrasmall GO nanosheets showed excellent biocompatibility of lower cytotoxicity and higher cellular uptake amount compared to the random large GO nanosheets. Therefore, the as-prepared uniform ultrasmall GO nanosheets could be explored as the ideal nanocarriers for drug delivery and intracellular fluorescent nanoprobe.Keywords: cellular uptake; cytotoxicity; graphene oxide; nanocarrier; stability; ultrasmall;
Co-reporter:Yuanqing Zhang, Xiaoping Xu, Lu Wang, Jun Lin, Ying Zhu, Zhi Guo, Yanhong Sun, Hua Wang, Yun Zhao, Renzhong Tai, Xiaohan Yu, Chunhai Fan and Qing Huang
Chemical Communications 2013 vol. 49(Issue 88) pp:10388-10390
Publication Date(Web):13 Sep 2013
DOI:10.1039/C3CC46057F
We present a bioprobe for synchrotron X-ray fluorescence imaging based on dendrimer–folate–copper conjugates. The metal nanoclusters within a dendrimer exhibit excellent FR-targeting properties in KB cells. It could be used as a new multifunction bioprobe for synchrotron X-ray fluorescence mapping.
Co-reporter:Jinming Zhao;Bo Deng;Min Lv;Jingye Li;Yujie Zhang;Haiqing Jiang;Cheng Peng;Jiang Li;Jiye Shi;Chunhai Fan
Advanced Healthcare Materials 2013 Volume 2( Issue 9) pp:1259-1266
Publication Date(Web):
DOI:10.1002/adhm.201200437
Abstract
Graphene oxide (GO) is an excellent bacteria-killing nanomaterial. In this work, macroscopic applications of this promising nanomaterial by fixing GO sheets onto cotton fabrics, which possess strong antibacterial property and great laundering durability, are reported. The GO-based antibacterial cotton fabrics are prepared in three ways: direct adsorption, radiation-induced crosslinking, and chemical crosslinking. Antibacterial tests show that all these GO-containing fabrics possess strong antibacterial property and could inactivate 98% of bacteria. Most significantly, these fabrics can still kill >90% bacteria even after being washed for 100 times. Also importantly, animal tests show that GO-modified cotton fabrics cause no irritation to rabbit skin. Hence, it is believed that these flexible, foldable, and re-usable GO-based antibacterial cotton fabrics have high promise as a type of new nano-engineered antibacterial materials for a wide range of applications.
Co-reporter:Feng Bianying, Guo Linjie, Wang Lihua, Li Fan, Lu Jianxin, Gao Jimin, Fan Chunhai, and Huang Qing
Analytical Chemistry 2013 Volume 85(Issue 16) pp:7732
Publication Date(Web):July 18, 2013
DOI:10.1021/ac4009463
Analysis of peptide–receptor interactions provides insights for understanding functions of proteins in cells. In this work, we report the development of a fluorescent biosensor for the analysis of peptide–receptor interactions using graphene oxide (GO) and fluorescein isothiocyanate (FITC)-labeled octreotide (FOC). Octreotide is a synthesized cyclic peptide with somatostatin-like bioactivity that has been clinically employed. FOC exhibits high adsorption affinity for GO, and its binding results in efficient fluorescence quenching of FITC. Interestingly, the specific binding of the antibody anti-octreotide (AOC) with FOC competitively releases FOC from the GO surface, leading to the recovery of fluorescence. By using this GO-based fluorescent platform, we can detect AOC with a low detection limit of 2 ng/mL. As a step further, we employ this GO–FOC biosensor to image somatostatin receptor subtype 2 overexpressed AR42J tumor cells, which demonstrates high promise for molecular imaging in cancer diagnosis.
Co-reporter:Jichao Zhang, Xiaoqing Cai, Yi Zhang, Xiaoming Li, Wenxin Li, Yangchao Tian, Aiguo Li, Xiaohan Yu, Chunhai Fan and Qing Huang
Analytical Methods 2013 vol. 5(Issue 23) pp:6611-6616
Publication Date(Web):10 Sep 2013
DOI:10.1039/C3AY41121D
Understanding the internalization of nanoparticles in cells is of great interest for diagnostic and therapeutic applications. We investigated the cellular uptake and distribution of TiO2 nanoparticles by high lateral resolution transmission electron microscopy (TEM) and transmission X-ray microscopy. TEM results showed that TiO2 nanoparticle internalization mostly occurred via endocytosis and the nanoparticles were distributed in the cytoplasm. 3D reconstructed tomography also confirmed that TiO2 nanoparticle aggregates were mainly distributed over the cell membrane surface.
Co-reporter:Ping Wang, Hao Pei, Ying Wan, Jiang Li, Xinhua Zhu, Yan Su, Chunhai Fan and Qing Huang
Nanoscale 2012 vol. 4(Issue 21) pp:6739-6742
Publication Date(Web):29 Aug 2012
DOI:10.1039/C2NR31705B
We have developed a microcantilever based sensor array which can be functionalized with mercapto-compounds to detect proteins. Linear discriminant analysis (LDA) is used to differentiate the cantilever deflection patterns. It is concluded that more sensors give better separating capacity and the COOH and Si–OCH3 groups are important factors in protein recognition.
Co-reporter:Min Lv, Yujie Zhang, Le Liang, Min Wei, Wenbing Hu, Xiaoming Li and Qing Huang
Nanoscale 2012 vol. 4(Issue 13) pp:3861-3866
Publication Date(Web):14 May 2012
DOI:10.1039/C2NR30407D
Graphene oxide (GO), has created an unprecedented opportunity for development and application in biology, due to its abundant functional groups and well water solubility. Recently, the potential toxicity of GO in the environment and in humans has garnered more and more attention. In this paper, we systematically studied the cytotoxicity of GO nanosheets via examining the effect of GO on the morphology, viability and differentiation of a human neuroblastoma SH-SY5Y cell line, which was an ideal model used to study neuronal disease in vitro. The results suggested that GO had no obvious cytotoxicity at low concentration (<80 μg mL−1) for 96 h, but the viability of cells exhibited dose- and time-dependent decreases at high concentration (≥80 μg mL−1). Moreover, GO did not induce apoptosis. Very interestingly, GO significantly enhanced the differentiation of SH-SY5Y induced-retinoic acid (RA) by evaluating neurite length and the expression of neuronal marker MAP2. These data provide a promising application for neurodegenerative diseases.
Co-reporter:Bowu Zhang, Yujie Zhang, Cheng Peng, Ming Yu, Linfan Li, Bo Deng, Pengfei Hu, Chunhai Fan, Jingye Li and Qing Huang
Nanoscale 2012 vol. 4(Issue 5) pp:1742-1748
Publication Date(Web):10 Jan 2012
DOI:10.1039/C2NR11724J
Herein, we report a facile approach to decorate graphene oxide (GO) sheets with poly(vinyl acetate) (PVAc) by γ-ray irradiation-induced graft polymerization. The content of PVAc in the obtained sample, i.e., PVAc grafted GO (GO-g-PVAc) is calculated by the loss weight in thermogravimetric analysis (TGA) curves. A GO-g-PVAc sample with a degree of grafting (DG) of 28.5% was well dispersed in common organic solvents and the dispersions obtained were extremely stable at room temperature without any aggregation, even after standing for 2 months. The excellent dispersibility and stability of GO-g-PVAc in common organic solvents are readily rationalized in terms of the full coverage of PVAc chains and solvated layer formation on graphene oxide sheets surface, which weakens the interlaminar attraction of GO sheets. This approach presents a facile route for the preparation of dispersible GO and shows great potential in the preparation of graphene-based composites by solution-processes.
Co-reporter:Zihao Wang, Zhilei Ge, Xiaoxue Zheng, Nan Chen, Cheng Peng, Chunhai Fan and Qing Huang
Nanoscale 2012 vol. 4(Issue 2) pp:394-399
Publication Date(Web):16 Nov 2011
DOI:10.1039/C1NR11174D
Graphene is an increasingly important nanomaterial exhibiting great promise in the area of nanotechnology. In this study, the azide-functionalized graphene derivative was synthesized as the ‘click’ reagent for preparation of polyvalent DNA–graphene conjugates, which provide an effective and stable platform to construct new functional nano-architectures. Assembled with Au nanoparticles, the prepared Au–DNA–graphene nanocomplex exhibits excellent stability that could prevent the nanocomplex from being destroyed by surfactants. Assembled with DNA tetrahedron-structured probes (TSPs), the nanocomplex displays outstanding sensitive electrochemiluminescence properties, which might be used as a biosensor for DNA detection. Therefore, this DNA–graphene conjugates could be explored as the assembly unit for advanced DNA nano-architectures in the field of DNA nanotechnology.
Co-reporter:Nan Chen, Yao He, Yuanyuan Su, Xiaoming Li, Qing Huang, Haifeng Wang, Xiangzhi Zhang, Renzhong Tai, Chunhai Fan
Biomaterials 2012 33(5) pp: 1238-1244
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.10.070
Co-reporter:Min Wei;Dr. Nan Chen;Dr. Jiang Li;Min Yin;Le Liang; Yao He; Haiyun Song; Chunhai Fan; Qing Huang
Angewandte Chemie International Edition 2012 Volume 51( Issue 5) pp:1202-1206
Publication Date(Web):
DOI:10.1002/anie.201105187
Co-reporter:YuJie Zhang;MaKe Geng;Huan Zhang;Yao He;Cheng Peng
Science Bulletin 2012 Volume 57( Issue 23) pp:3086-3092
Publication Date(Web):2012 August
DOI:10.1007/s11434-012-5333-6
Graphene and its derivative, graphene oxide (GO) have been substantively used as the main framework for dispersing or building nanoarchitectures because of their excellent properties in electronics and catalysis. The requirement to obtain superior graphene-metal hybrid nanomaterials has led us to explore a facile way to design 4-aminobenzenethiol/1-hexanethiolate-protected gold nanoparticles (aAuNPs)-functionalized graphene oxide composite (aAuNPs-GO) in solution. We demonstrate that when aAuNPs with amino groups are exposed to GO, well-dispersed coverage of Au nanoparticles are mainly observed on the edge of GO sheet. In contrast, when 1-hexanethiolate-protected gold nanoparticles (hAuNPs) without amino groups are exposed to GO, hAuNPs simply aggregate on the surface of GO. This indicates that amino groups located on the surface of Au nanoparticles are an essential prerequisite for attachment of nearly monodispersed aAuNPs. The strategy described here for the fabrication of aAuNPs-GO provides a straightforward approach to develop graphene-based nanocomposites with undamaged sheets structure and good solubility and also improve the conductivity of GO sheets evidently.
Co-reporter:Xiaoyong Zhang, Jilei Yin, Cheng Peng, Weiqing Hu, Zhiyong Zhu, Wenxin Li, Chunhai Fan, Qing Huang
Carbon 2011 Volume 49(Issue 3) pp:986-995
Publication Date(Web):March 2011
DOI:10.1016/j.carbon.2010.11.005
We determined the distribution and biocompatibility of graphene oxide (GO) in mice by using radiotracer technique and a series of biological assays. Results showed that GO was predominantly deposited in the lungs, where it was retained for a long time. Compared with other carbon nanomaterials, GO exhibited long blood circulation time (half-time 5.3 ± 1.2 h), and low uptake in reticuloendothelial system. No pathological changes were observed in examined organs when mice were exposed to 1 mg kg−1 body weight of GO for 14 days. Moreover, GO showed good biocompatibility with red blood cells. These results suggested that GO might be a promising material for biomedical applications, especially for targeted drug delivery to the lung. However, due to its high accumulation and long time retention, significant pathological changes, including inflammation cell infiltration, pulmonary edema and granuloma formation were found at the dosage of 10 mg kg−1 body weight. More attention should be paid to the toxicity of GO.Graphical abstractResearch highlights► GO can be effectively labeled with 188Re. ► 188Re–GO was predominantly deposited in the lungs. ► GO shows good biocompatibility to targeted organs. ► GO shows good biocompatibility to RBC. ► Provided basic information for toxicity assessment and biomedical applications.
Co-reporter:Wenbing Hu, Cheng Peng, Min Lv, Xiaoming Li, Yujie Zhang, Nan Chen, Chunhai Fan, and Qing Huang
ACS Nano 2011 Volume 5(Issue 5) pp:3693
Publication Date(Web):April 18, 2011
DOI:10.1021/nn200021j
Graphene is a single layer of sp2-bonded carbons that has unique and highly attractive electronic, mechanical, and thermal properties. Consequently, the potential impact of graphene and its derivatives (e.g., graphene oxide, GO) on human and environmental health has raised considerable concerns. In this study, we have carried out a systematic investigation on cellular effects of GO nanosheets and identified the effect of fetal bovine serum (FBS), an often-employed component in cell culture medium, on the cytotoxicity of GO. At low concentrations of FBS (1%), human cells were sensitive to the presence of GO and showed concentration-dependent cytotoxicity. Interestingly, the cytotoxicity of GO was greatly mitigated at 10% FBS, the concentration usually employed in cell medium. Our studies have demonstrated that the cytotoxicity of GO nanosheets arises from direct interactions between the cell membrane and GO nanosheets that result in physical damage to the cell membrane. This effect is largely attenuated when GO is incubated with FBS due to the extremely high protein adsorption ability of GO. The observation of this FBS-mitigated GO cytotoxicity effect may provide an alternative and convenient route to engineer nanomaterials for safe biomedical and environmental applications.Keywords: cell membrane damage; cytotoxicity; graphene oxide; protein adsorbability
Co-reporter:Jiang Li, Hao Pei, Bing Zhu, Le Liang, Min Wei, Yao He, Nan Chen, Di Li, Qing Huang, and Chunhai Fan
ACS Nano 2011 Volume 5(Issue 11) pp:8783
Publication Date(Web):October 11, 2011
DOI:10.1021/nn202774x
Designed oligonucleotides can self-assemble into DNA nanostructures with well-defined structures and uniform sizes, which provide unprecedented opportunities for biosensing, molecular imaging, and drug delivery. In this work, we have developed functional, multivalent DNA nanostructures by appending unmethylated CpG motifs to three-dimensional DNA tetrahedra. These small-sized functional nanostructures are compact, mechanically stable, and noncytotoxic. We have demonstrated that DNA nanostructures are resistant to nuclease degradation and remain substantially intact in fetal bovine serum and in cells for at least several hours. Significantly, these functional nanostructures can noninvasively and efficiently enter macrophage-like RAW264.7 cells without the aid of transfection agents. After they are uptaken by cells, CpG motifs are recognized by the Toll-like receptor 9 (TLR9) that activates downstream pathways to induce immunostimulatory effects, producing high-level secretion of various pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12. We also show that multivalent CpG motifs greatly enhance the immunostimulatory effect of the nanostructures. Given the high efficacy of these functional nanostructures and their noncytotoxic nature, we expect that DNA nanostructures will become a promising tool for targeted drug delivery.Keywords: DNA nanotechnology; immunostimulation; nanomedicine; tetrahedral; transfection
Co-reporter:Min Lv;Shao Su;Yao He;Wenbing Hu;Di Li;Chunhai Fan;Shuit-Tong Lee
Advanced Materials 2010 Volume 22( Issue 48) pp:5463-5467
Publication Date(Web):
DOI:10.1002/adma.201001934
Co-reporter:Make Geng, Yujie Zhang, Qing Huang, Bowu Zhang, Qingnuan Li, Wenxin Li, Jingye Li
Carbon 2010 Volume 48(Issue 12) pp:3570-3574
Publication Date(Web):October 2010
DOI:10.1016/j.carbon.2010.05.055
Gold nanoparticles (GNPs) with attached C60 molecules (C60-GNPs) were prepared through the amination reaction of fullerene C60 with peripheral amino groups located on the surface of gold. Molecules of 4-aminobenzenethiol/1-hexanethiol containing amino groups were introduced onto the surface of gold by the reduction of a gold salt (HAuCl4) with sodium borohydride (NaBH4) in a one-pot way, which was accompanied by anchoring of the targeted thiol mixture on the gold cluster by Au–S bonds. This simple system avoids many difficult reactions and purification processes and does not involve a complicated chemical modification of C60 and exchange reactions of GNPs.
Co-reporter:Jing Li, Ying Zhu, Wenxin Li, Xiaoyong Zhang, Yan Peng, Qing Huang
Biomaterials 2010 31(32) pp: 8410-8418
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.07.058
Co-reporter:Wenbing Hu, Cheng Peng, Weijie Luo, Min Lv, Xiaoming Li, Di Li, Qing Huang and Chunhai Fan
ACS Nano 2010 Volume 4(Issue 7) pp:4317
Publication Date(Web):July 1, 2010
DOI:10.1021/nn101097v
Graphene is a monolayer of tightly packed carbon atoms that possesses many interesting properties and has numerous exciting applications. In this work, we report the antibacterial activity of two water-dispersible graphene derivatives, graphene oxide (GO) and reduced graphene oxide (rGO) nanosheets. Such graphene-based nanomaterials can effectively inhibit the growth of E. coli bacteria while showing minimal cytotoxicity. We have also demonstrated that macroscopic freestanding GO and rGO paper can be conveniently fabricated from their suspension via simple vacuum filtration. Given the superior antibacterial effect of GO and the fact that GO can be mass-produced and easily processed to make freestanding and flexible paper with low cost, we expect this new carbon nanomaterial may find important environmental and clinical applications.Keywords: antibacterial activity; graphene oxide; graphene oxide paper; minimal cytotoxicity; reduced graphene oxide
Co-reporter:Weijie Luo, Changfeng Zhu, Shao Su, Di Li, Yao He, Qing Huang, and Chunhai Fan
ACS Nano 2010 Volume 4(Issue 12) pp:7451
Publication Date(Web):November 30, 2010
DOI:10.1021/nn102592h
Size and shape of nanoparticles are generally controlled by external influence factors such as reaction temperature, time, precursor, and/or surfactant concentration. Lack of external influence may eventually lead to unregulated growth of nanoparticles and possibly loss of their nanoscale properties. Here we report a gold nanoparticle (AuNPs)-based self-catalyzed and self-limiting system that exploits the glucose oxidase-like catalytic activity of AuNPs. We find that the AuNP-catalyzed glucose oxidation in situ produces hydrogen peroxide (H2O2) that induces the AuNPs’ seeded growth in the presence of chloroauric acid (HAuCl4). This crystal growth of AuNPs is internally regulated via two negative feedback factors, size-dependent activity decrease of AuNPs and product (gluconic acid)-induced surface passivation, leading to a rapidly self-limiting system. Interestingly, the size, shape, and catalytic activities of AuNPs are simultaneously controlled in this system. We expect that it provides a new method for controlled synthesis of novel nanomaterials, design of “smart” self-limiting nanomedicine, as well as in-depth understanding of self-limiting systems in nature.Keywords: catalytic activity; crystal growth; glucose oxidase; gold nanoparticles; self-limiting
Co-reporter:Yuanyuan Su, Mei Hu, Chunhai Fan, Yao He, Qingnuan Li, Wenxin Li, Lian-hui Wang, Pingping Shen, Qing Huang
Biomaterials 2010 31(18) pp: 4829-4834
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.02.074
Co-reporter:Ying Zhu, Wenxin Li, Qingnuan Li, Yuguo Li, Yufeng Li, Xiaoyong Zhang, Qing Huang
Carbon 2009 Volume 47(Issue 5) pp:1351-1358
Publication Date(Web):April 2009
DOI:10.1016/j.carbon.2009.01.026
To explore the effects of the novel properties of carbon nanoparticles (CNPs) on cytotoxicity, the adsorption of serum proteins in cell culture medium on multi-walled carbon nanotubes and three kinds of carbon blacks was investigated. The uptake of CNPs by Hela cells was measured quantitatively using 99mTc radionuclide labeling and tracing techniques, and the dependence of CNPs uptake on serum proteins was examined. The cytotoxicity of CNPs in medium with and without serum was assayed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. It was found that cellular uptake was much higher in cells exposed to CNPs in serum-free culture medium than those in culture medium with serum. Serum proteins adsorbed on CNPs attenuated the inherent cytotoxicity of CNPs, and the extent of toxicity attenuation increased with increasing amounts of serum proteins adsorbed on CNPs. The possible reasons responsible for the considerable influence of serum proteins on cytotoxicity were indicated.
Co-reporter:Yuanyuan Su, Jing-ying Xu, Pingping Shen, Jiang Li, Lihua Wang, Qingnuan Li, Wenxin Li, Guo-tong Xu, Chunhai Fan, Qing Huang
Toxicology (10 March 2010) Volume 269(Issues 2–3) pp:155-159
Publication Date(Web):10 March 2010
DOI:10.1016/j.tox.2009.11.015
We reported the studies of aggregation, cellular uptake and cytotoxicity of C60(OH)x, one of important water-soluble fullerene derivatives. The results showed C60(OH)x was smaller in size but harder to go into cells in the media with serum. Moreover, C60(OH)x showed severe toxicity to Chinese hamster lung and Chinese hamster ovary cells, but almost no effect on L929 cells, which implied that the cytotoxicity of C60(OH)x was cell type specific. Flow cytometry was used to examine the precise effect of C60(OH)x on the cell cycle and found cells was blocked at G1 phase. These results are expected to be helpful to understand the toxicity of fullerene derivatives.
Co-reporter:Yuanqing Zhang, Xiaoping Xu, Lu Wang, Jun Lin, Ying Zhu, Zhi Guo, Yanhong Sun, Hua Wang, Yun Zhao, Renzhong Tai, Xiaohan Yu, Chunhai Fan and Qing Huang
Chemical Communications 2013 - vol. 49(Issue 88) pp:NaN10390-10390
Publication Date(Web):2013/09/13
DOI:10.1039/C3CC46057F
We present a bioprobe for synchrotron X-ray fluorescence imaging based on dendrimer–folate–copper conjugates. The metal nanoclusters within a dendrimer exhibit excellent FR-targeting properties in KB cells. It could be used as a new multifunction bioprobe for synchrotron X-ray fluorescence mapping.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 23) pp:
Publication Date(Web):
DOI:10.1039/C3AY41121D
Understanding the internalization of nanoparticles in cells is of great interest for diagnostic and therapeutic applications. We investigated the cellular uptake and distribution of TiO2 nanoparticles by high lateral resolution transmission electron microscopy (TEM) and transmission X-ray microscopy. TEM results showed that TiO2 nanoparticle internalization mostly occurred via endocytosis and the nanoparticles were distributed in the cytoplasm. 3D reconstructed tomography also confirmed that TiO2 nanoparticle aggregates were mainly distributed over the cell membrane surface.
