Co-reporter:Zhicheng Pan, Danxuan Fang, Nijia Song, Yuanqing Song, Mingming Ding, Jiehua Li, Feng Luo, Hong TanQiang Fu
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 3) pp:
Publication Date(Web):December 28, 2016
DOI:10.1021/acsami.6b14339
Polymeric micelles containing cationic gemini quaternary ammonium (GQA) groups have shown enhanced cellular uptake and efficient drug delivery, while the incorporation of poly(ethylene glycol) (PEG) corona can potentially reduce the absorption of cationic carriers by opsonic proteins and subsequent uptake by mononuclear phagocytic system (MPS). To understand the interactions of GQA and PEG groups and their effects on the biophysicochemical characteristics of nanocarriers, a series of polyurethane micelles containing GQA and different molecular weights of PEG were prepared and carefully characterized. It was found that the GQA and PEG groups are unevenly distributed on the micellar surface to form two kinds of hydrophilic domains. As a result, the particle surface with some defects cannot be completely shielded by the PEG corona. Despite this, the longer PEG chains with a brush conformation provide superior stabilization and steric repulsion against the absorption of proteins and, thus, can reduce the cytotoxicity, protein absorption, and MPS uptake of micelles to some extent. This study provides a new understanding on the interactions between PEG chains and cationic groups and a guideline for the design and fabrication of safe and effective drug delivery systems.Keywords: cellular uptake; Gemini cation; PEG; phagocytosis; polyurethane micelles; surface distribution;
Co-reporter:Ni-jia Song;Li-juan Zhou;Wen-kai Liu;Xue-ling He
Chinese Journal of Polymer Science 2017 Volume 35( Issue 8) pp:909-923
Publication Date(Web):25 June 2017
DOI:10.1007/s10118-017-1952-3
Polyurethane micelles (PM)-based nanovehicles have shown great potential in targeted delivery of therapeutics and diagnostics into tumors. However, the pathways of PMs entering cancer cells and the action mechanism of targeting ligands have yet to be understood. In this contribution, the actively-targeted PM were developed using trastuzumab as a model targeting group. It was found that PM were mainly taken up by SKOV-3 tumor cells via a micropinocytosis process, while the incorporation of trastuzumab to PM enabled a receptor-mediated endocytosis of nanocarriers in cancer cells, leading to more efficient cell entry and enhanced anticancer efficacy of chemotherapeutic drugs both in vitro and in vivo. This study is advantageous to the understanding of the action mechanism of trastuzumab, and significant for the construction of improved formulations for targeted delivery and precise therapy.
Co-reporter:Yi Zhang;Wei He;Jiehua Li;Kunjie Wang;Jianshu Li;Qiang Fu
Materials Chemistry Frontiers 2017 vol. 1(Issue 2) pp:361-368
Publication Date(Web):2017/02/16
DOI:10.1039/C6QM00039H
In this study, a series of waterborne biodegradable polyurethanes with antibacterial and biocompatible properties were developed. To obtain these polyurethanes, lysine-derivative gemini quaternary ammonium salt (GQAS) chain extenders with different hydrophobic alkyl chain lengths (named EGn, where n = 8, 12, 16; the hydrophobic alkyl chain length of GQAS) were designed and synthesized. Then, waterborne biodegradable polyurethanes (PCLPUn) were prepared using isophorone diisocyanate (IPDI), poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), L-lysine and EGn. The antibacterial activities of these EGn and PCLPUn emulsions were evaluated by a minimal inhibitory concentration (MIC) method, and the antibacterial and antifouling functionalities of the PCLPUn film surfaces were confirmed by a contact-active antibacterial and culture-based method using both Gram-positive and Gram-negative bacteria. The in vitro degradation and cytotoxicity of these obtained polyurethanes were also systematically investigated. These results indicated that the PCLPUn films possessed good antibacterial and antifouling abilities, biodegradability, and good biocompatibility. Notably, PCLPU12 shows the best antibacterial activity and cytocompatibility. Such antibacterial materials could be degraded to non-toxic components, and potentially be widely used in medical and environmental applications, especially as biodegradable coatings of surgical equipment and medical implants.
Co-reporter:Jing Wei, Xiaoyu Shuai, Rui Wang, Xueling He, Yiwen Li, Mingming Ding, Jiehua Li, Hong Tan, Qiang Fu
Biomaterials 2017 Volume 145(Volume 145) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.biomaterials.2017.08.005
Targeted delivery of therapeutics and diagnostics using nanotechnology holds great promise to minimize the side effects of conventional chemotherapy and enable specific and real-time detection of diseases. To realize this goal, we report a clickable and imageable nanovehicle assembled from multiblock polyurethanes (MPUs). The soft segments of the polymers are based on detachable poly(ethylene glycol) (PEG) and degradable poly(ε-caprolactone) (PCL), and the hard segments are constructed from lysine- and cystine-derivatives bearing reduction-responsive disulfide linkages and click-active alkynyl moieties, allowing for post-conjugation of targeting ligands via a click chemistry. It was found that the cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage (BPEG) could act as an on-off switch, which is capable of activating the clicked targeting ligands under extracellular acidic condition, followed by triggering the core degradation and payload release within tumor cells. In combination with superparamagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T2 relaxation in vitro, as well as magnetically guided MR imaging and multimodal targeting of therapeutics to tumor precisely, leading to significant inhibition of cancer with minimal side effect. This work provides a safe and versatile platform for the further development of smart theranostic systems for potential magnetically-targeted and imaging-guided personalized medicine.Download high-res image (337KB)Download full-size image
Co-reporter:Nijia Song, Lijuan Zhou, Jiehua Li, Zhicheng Pan, Xueling He, Hong Tan, Xinyuan Wan, Jianshu Li, Rong Ran and Qiang Fu
Nanoscale 2016 vol. 8(Issue 14) pp:7711-7722
Publication Date(Web):15 Mar 2016
DOI:10.1039/C6NR00859C
A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases.
Co-reporter:Yuanqing Song, Yunlong Gao, Xinyuan Wan, Feng Luo, Jiehua Li, Hong Tan and Qiang Fu
RSC Advances 2016 vol. 6(Issue 21) pp:17336-17344
Publication Date(Web):04 Feb 2016
DOI:10.1039/C5RA27081B
Complications such as thromboembolism and bacterial infection, arising from the widespread use of implanted medical devices, are serious problems for current clinical treatment. In this work, dual-functional anticoagulant and antibacterial blend coatings were designed and fabricated from gemini quaternary ammonium salt waterborne polyurethane (GWPU) emulsion and heparin aqueous solution. The results demonstrate that the L-lysine-derivative gemini quaternary ammonium salt (GQAS) in GWPU endows the coating with excellent non-releasing antibacterial ability and simultaneously the release of heparin provides superior anticoagulant activity. Moreover, the controlled release of heparin is achieved by the ionic interaction between the positive charge in GQAS and the negative charge in heparin. On the basis of the dual-functional anticoagulant and antibacterial properties of GWPU/heparin blend coatings, this work proposes a facile strategy to achieve syncretic performances in biomaterials, and these coatings would have the potential to improve the application of implanted devices.
Co-reporter:Yan-Chao Wang, Fang Fang, Ying-Ke Wu, Xiao-Lin Ai, Ting Lan, Rui-Chao Liang, Yu Zhang, Narasimha Murthy Trishul, Min He, Chao You, Chuan Yu and Hong Tan
RSC Advances 2016 vol. 6(Issue 5) pp:3840-3849
Publication Date(Web):22 Dec 2015
DOI:10.1039/C5RA20181K
Rehabilitation from traumatic brain injury (TBI) is a significant challenge for neurosurgeons as no effective strategies for cerebral tissue reconstruction can be adopted in clinical applications. To explore an appropriate method for cerebral tissue regeneration, we developed a type of waterborne biodegradable polyurethane (WBPU) 3-dimentional (3D) porous scaffold. Two types of WBPU (WBPU17 and WBPU25) 3D scaffolds were prepared based on different molar content of poly ethylene glycol (PEG) within the scaffolds. The porosity of WBPU17 and WBPU25 scaffolds was 83.29% ± 0.53% and 86.72% ± 0.78%, respectively. The mean pore size of the WBPU17 and WBPU25 scaffolds was 20.10 μm and 22.18 μm, respectively. No pronounced cytotoxicity was noticed for the rat glial cells when treated with degradation liquid of the WBPU17 and WBPU25 scaffold. Moreover, both the WBPU17 and WBPU25 scaffold treated groups showed stronger expression of neuronal growth associated protein (GAP43) and synaptophysin, indicating better nerve regeneration in the experiment groups compared to none in the scaffold control group in the rat TBI model. In addition, functional recovery also displayed a satisfactory result in the WBPU17 and WBPU25 scaffold treated groups. Overall, the WBPU25 scaffold had better performance than of the WBPU17 scaffold. The results of our experiments proved that the WBPU 3D porous scaffold, especially the WBPU25 scaffold, is a promising therapeutic implant for both cerebral tissue regeneration and neural functional recovery in TBI.
Co-reporter:Yuan-qing Song;Yun-long Gao;Zhi-cheng Pan;Yi Zhang
Chinese Journal of Polymer Science 2016 Volume 34( Issue 6) pp:679-687
Publication Date(Web):2016 June
DOI:10.1007/s10118-016-1787-3
In this study, to improve hemocompatibility of biomedical materials, a waterborne polyurethane (WPU)/heparin release coating system (WPU/heparin) is fabricated via simply blending biodegradable WPU emulsions with heparin aqueous solutions. The surface compositions and hydrophilicity of these WPU/heparin blend coatings are characterized by attenuated total reflectance infrared spectroscopy (ATR-FTIR) and water contact angle measurements. These WPU/heparin blend coatings show effectively controlled release of heparin, as determined by the toluidine blue method. Furthermore, the biocompatibility and anticoagulant activity of these blend coatings are evaluated based on the protein adsorption, platelet adhesion, activated partial thromboplastin time (APTT), thrombin time (TT), hemolysis, and cytotoxicity. The results indicate that better hemocompatibility and cytocompatilibity are obtained due to blending heparin into this waterborne polyurethane. Thus, the WPU/heparin blend coating system is expected to be valuable for various biomedical applications.
Co-reporter:Hualei Chu;Yuanqing Song;Jiehua Li;Feng Luo
Colloid and Polymer Science 2016 Volume 294( Issue 2) pp:433-439
Publication Date(Web):2016 February
DOI:10.1007/s00396-015-3798-y
Polyisoprene (PI) is the main component of natural rubber. To imitate natural rubber and understand the function of phospholipid in natural rubber, a novel phosphatidylcholine (PC)-modified polyisoprene (PI-pc) is synthesized using a PC and a commercial PI. The PI is firstly brominated by N-bromosuccinimide, and then, diethyl malonate is introduced as a branch chain of PI. In sequence, the PC is imported into the branch chain of PI via condensation of the activated ester terminals in diethyl malonate and the amino terminals in PC to obtain the desired product PI-pc. The bulk structure of the prepared PI-pc is carefully characterized with nuclear magnetic resonance spectra (1H and 31P NMR), Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatograph (GPC), and differential scanning calorimetry (DSC). The introduction of PC to the branch chain of PI increases the molecular weight and also the glass transition (Tg) of the PI. The increment of Tgs and melting enthalpy for the PI-pcs from both solution and emulsion indicates that the attached PC is beneficial to the self-assembly of PI chains and thus promotes the crystallization. Our present work provides a new method for importing PC to PI to imitate natural rubber, and also, the results could be a footstone for us to explore the effect of phospholipid on the property of natural rubber.
Co-reporter:Nijia Song, Zhicheng Pan, Jiehua Li, Hong Tan, Qiang Fu
Nanomedicine: Nanotechnology, Biology and Medicine 2016 Volume 12(Issue 2) pp:463-464
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.051
Co-reporter:Zhicheng Pan, Yanji Ren, Nijia Song, Yuanqing Song, Jiehua Li, Xueling He, Feng Luo, Hong Tan, and Qiang Fu
Biomacromolecules 2016 Volume 17(Issue 6) pp:
Publication Date(Web):April 30, 2016
DOI:10.1021/acs.biomac.6b00375
A challenge in the development of multifunctional drug delivery systems is to establish a reasonable and effective synthetic route for multifunctional polymer preparation. Herein, we propose a unique protocol to prepare multifunctional micelles by a cross-assembly process using three different functional polyurethanes incorporating acidic sensitive hydrazone, folic acid for active targeting, and gemini quaternary ammonium (GQA) as efficient cell uptake ligands, respectively. These multifunctional mixed micelles (GFHPMs) have been endowed tunable particle sizes and zeta potential and a unique three-order-layer cross-assemble structure. Their drug-loading contents have been significantly improved, and drug release profiles displayed controlled release of their payloads under acid condition. The folate and GQA ligands showed a synergistic effect to enhance the cell uptake. Biodistribution and antitumor effect of these micelles were systematically investigated in vivo, the mixed micelles could penetrate into the depths of tumors, and drug concentrations in tumors reached the maximum of 6.5% ID/g at 24 h, resulting in an excellent therapeutic effect that the volumes of tumors treated with GFHPM are five times smaller than those treated with blank micelles. Our present work provides an effective approach to the design of multifunctional nanocarriers for tumor-targeted and programmed intracellular drug delivery.
Co-reporter:Xinyuan Wan, Yi Zhang, Ya Deng, Qin Zhang, Jiehua Li, Kunjie Wang, Jianshu Li, Hong Tan and Qiang Fu
Soft Matter 2015 vol. 11(Issue 21) pp:4197-4207
Publication Date(Web):17 Apr 2015
DOI:10.1039/C5SM00380F
In this paper, to investigate the effects of interactions between poly(quaternary ammonium) salts (PQAs) and poly(ethylene glycol) on their mixed micellar surface structures and properties under spontaneous conditions, a series of PQAs were first designed and synthesized by atom transfer radical polymerization (ATRP) using 2-(dimethylamino) ethyl methacrylate (DMAEMA) quaternized by bromobutane, bromooctane, and bromododecane, respectively. Poly(poly(ethylene glycol) methyl ether methacrylate) (PPEG) with a similar degree of polymerization was also prepared using poly(ethylene glycol) methyl ether methacrylate by ATRP. Next, these PQAs were mixed with an equal weight of PPEG in water to cross-assemble into mixed micelles. The structures and features of these mixed micelles were characterized by fluorescence measurements, transmission electron microscopy (TEM), dynamic light scattering (DLS), phase analysis light scattering (PALS), proton nuclear magnetic resonance (1H NMR), and hydrogen–hydrogen correlation spectroscopy nuclear magnetic resonance (H–H COSY NMR). These results suggest that PQAs and PPEG mixtures can cross-assemble into mixed micelles with low CMC. The surface structures, particle sizes, size distributions, and zeta potentials of PQAs and PPEG mixtures can be tailored by varying the alkyl chain length in quaternary ammonium salts, and the alkyl chain length also influences the distribution and the alkyl chain orientation of quaternary ammonium salts on mixed micelle surfaces. In addition, cytotoxicity of these mixed micelles can be markedly reduced by PPEG compared with their corresponding PQAs, but their good antibacterial activities are still maintained to a certain degree, as evaluated by methyl tetrazolium assay (MTT) and minimum inhibitory concentration (MIC). Our present work provides a new avenue for the preparation of biocompatible and antibacterial materials for biomedical applications.
Co-reporter:Rui-Chao Liang, Fang Fang, Yan-Chao Wang, Ni-Jia Song, Jie-Hua Li, Cheng-Jian Zhao, Xing-Chen Peng, Ai-Ping Tong, Yuan Fang, Min He, Chao You and Hong Tan
RSC Advances 2015 vol. 5(Issue 8) pp:6160-6171
Publication Date(Web):12 Dec 2014
DOI:10.1039/C4RA09908G
Brain drug delivery is still facing significant challenges due to the low permeability of the blood–brain barrier (BBB). To overcome such an insurmountable obstacle, we developed gemini quaternary ammonium (GQA) as a cell penetrating molecule incorporated into biodegradable multiblock poly(ε-caprolactone urethanes)s (BMPUs) drug nanocarriers for improvement of drug accumulation in brain parenchyma. The zeta potential of Dox-loaded GQA-BMPUs micelles was around 26 mV with a mean particle size near 100 nm. It was found that GQA-BMPUs micelles achieved steadily time-dependent and concentration-dependent Dox accumulation in human brain microvascular endothelial cells (HBMECs) much higher than GQA-free BMPUs micelles and free Dox, as confirmed by flow cytometry and confocal laser scanning microscopy (CLSM) experiments. Meanwhile, no pronounced cytotoxicity was noticed in GQA-BMPUs micelles and GQA-free BMPUs micelles, and Dox associated cytotoxicity might be reduced once encapsulated into micelles. More importantly, CLSM of brain sections showed higher accumulation of Dox-loaded GQA-BMPUs micelles in the subcortical area after administrated intravenously, while no Dox accumulation was observed in either Dox-BMPUs micelles or free Dox formulation. Coupling with in vivo pharmacokinetics, biodistribution and histological toxicity studies, the results show that GQA introduced into drug nanocarriers is a promising avenue to transport therapeutic agents across BBB and improve brain drug accumulation.
Co-reporter:Wei He, Yi Zhang, Feng Luo, Jiehua Li, Ke Wang, Hong Tan and Qiang Fu
RSC Advances 2015 vol. 5(Issue 109) pp:89763-89770
Publication Date(Web):12 Oct 2015
DOI:10.1039/C5RA16714K
A series of novel non-releasing antibacterial polymer coatings, incorporating gemini quaternary ammonium salt modified waterborne polyurethane into a commercial poly(styrene-acrylate), were designed and prepared via a facile blending strategy. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and differential scanning calorimetry (DSC) results are used to prove the compatibility between the polyurethanes and poly(styrene-acrylate)s. X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) measurements are used to clarify the surface structure and properties of polymer coatings, indicating gemini quaternary ammonium salts (GQAS) attached onto waterborne polyurethane chains could migrate and aggregate onto surfaces of these polymer blending coatings. On the basis of the antibacterial characteristics of GQAS, these polymer blending coatings showed high efficiency in killing airborne bacteria, e.g. S. aureus and E. coli, in contact-killing tests. Thus, the antibacterial coatings and blending strategy are promising for the development of environmentally friendly materials.
Co-reporter:Zhicheng Pan, Hongye Hao, Yun Zhao, Jiehua Li, Hong Tan, Qiang Fu
Colloids and Surfaces B: Biointerfaces 2015 Volume 128() pp:36-43
Publication Date(Web):1 April 2015
DOI:10.1016/j.colsurfb.2015.02.012
•The moderate surface initiator density is conducive to the graft polymerization of fluorocarbon phospholipid macromonomer.•It was definitely demonstrated that the fluorocarbon phospholipid polymer brushes grafted on polyurethane films could self-assemble into biomimetic membranes under water environment.•The water exists within phospholipid polymers brushes as the “surrounding” water, which are favorable conditions for the native conformational state of proteins and cell membranes.To fabricate artificial biomembrane mimicking cell surfaces, hydrocarbon/fluorocarbon double-chain phospholipid macromonomer was grafted on polyurethane (PU) film surfaces by surface-initiated atom transfer radical polymerization (SI-ATRP). The surface structures of modified PU film surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and water contact angle measurement. The results indicate that initiator densities on these polymer film surfaces have a significant impact on graft polymerization of this fluorocarbon phospholipid macromonomer. The phospholipid polymer brushes grafted on PU film surfaces could self-assemble into biomimetic membranes under water environment, as demonstrated by liquid/liquid static contact angle measurement, atomic force spectroscopy (AFM), and attenuated total reflectance Fourier transform infrared (ATR-FTIR). These biomimetic membranes could maintain water within them as the “surrounding” water. Such would be favorable condition for the preservation of native conformational state of proteins and cell membranes. This work provides a new approach to fabricate biomimetic membranes on biomaterials surfaces.
Co-reporter:Yi Zhang;Yifan Li;Jiehua Li;Yunlong Gao;Kunjie Wang
Science Bulletin 2015 Volume 60( Issue 12) pp:1114-1121
Publication Date(Web):2015 June
DOI:10.1007/s11434-015-0811-2
To obtain an aqueous polymer system with good antibacterial properties, a series of gemini waterborne polyurethanes (GWPU) were designed and synthesized using isophorone diisocyanate, polyoxytetramethylene glycol, poly(ethylene glycol), L-lysine and a novel L-lysine-derivatized diamine containing gemini quaternary ammonium salt (EG12) without any other organic agent involved in the whole synthetic process. EG12 was first synthesized and characterized with proton nuclear magnetic resonance spectra and mass spectra. The antibacterial activities of EG12 and GWPU were evaluated by quantifying the minimal inhibitory concentration. The results indicated that the gemini quaternary ammonium chain extender EG12 and GWPU showed excellent antibacterial activity against a broad spectrum of gram-positive and gram-negative bacteria. This work provides a new and facile approach to prepare novel antibacterial materials, which could be applied as coatings in various fields to prevent microbial contamination.为了获得一种同时具有优异杀菌和防污效果的水性高分子材料,本文首先合成了一种gemini季铵盐二胺扩链剂(EG12),然后结合异佛尔酮二异氰酸酯(IPDI)、聚乙二醇(PEG)、L-赖氨酸和聚四氢呋喃醚二醇(PTMG),采用一种简单的方法,合成了一系列不同含量gemini季铵盐的抗菌水性聚氨酯乳液,并采用1H NMR,FTIR,DSC等对其结构进行了表征。通过最低抑菌浓度测试法(MIC)对所得gemini季铵盐EG12单体和抗菌水性聚氨酯乳液的抗菌性能进行表征,结果表明EG12和抗菌水性聚氨酯乳液对革兰氏阳性菌及革兰氏阴性菌都具有良好的广谱抗菌效果。本研究为制备防污杀菌新材料提供了一种新型、简单的方法和思路,此水性抗菌聚氨酯材料本身或与其它涂料共混作为涂层可广泛应用于医疗、食品包装、造纸、纤维等领域,用来阻止微生物污染。
Co-reporter:Dongsheng Tan, Zhen Li, Xuelin Yao, Chunlan Xiang, Hong Tan and Qiang Fu
Journal of Materials Chemistry A 2014 vol. 2(Issue 10) pp:1344-1353
Publication Date(Web):03 Dec 2013
DOI:10.1039/C3TB21473G
To study the influence of fluorinated surfaces and biomimetic surfaces on the improvement of the blood compatibility of polymers, three monomers containing a fluorinated tail and/or phosphorylcholine groups were designed and synthesized, and were then introduced into polyurethanes based on 4,4′-diphenylmethane diisocyanate (MDI), poly(tetramethylene glycol) (PTMG) and 1,4-butanediol (BDO) via end-capping. The bulk and surface characterization of the polyurethanes was carried out by dynamic mechanical analysis (DMA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopic analysis (XPS), atomic force microscope (AFM), and water contact angle measurements. The results indicate that the fluorocarbon chains can drive the phosphorylcholine groups to aggregate at the surface of polyurethane, and the two components show spontaneous arrangement to adapt to the environment when in contact with water. The preliminary evaluation of hemocompatibility was carried out via fibrinogen adsorption and platelet adhesion. The fluorocarbon chains and phosphorylcholine groups showed a synergistic effect on the improvement of hemocompatibility.
Co-reporter:Zhicheng Pan, Lunquan Yu, Nijia Song, Lijuan Zhou, Jiehua Li, Mingming Ding, Hong Tan and Qiang Fu
Polymer Chemistry 2014 vol. 5(Issue 8) pp:2901-2910
Publication Date(Web):24 Dec 2013
DOI:10.1039/C3PY01340E
In this study, a novel folate-conjugated chain extender (LDDFA) was designed and synthesized to enhance site-specific intracellular delivery of drug carriers against folate receptor overexpressing tumors. A series of biodegradable polyurethanes containing high folate content were prepared using poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) as soft segments, and 1,3-propanediol (PDO), L-lysine ethyl ester diisocyanate (LDI) and LDDFA as hard segments. The resultant polyurethanes were characterized with proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier-transform infrared (FTIR) spectroscopy and gel permeation chromatography (GPC). The folate contents were quantitatively analyzed with ultraviolet (UV) spectrophotometry. The folate-conjugated polymers could self-assemble into micelles with particularly loose hydrophobic cores and exhibiting low critical micelle concentration (CMC) in aqueous solution, in which folic acid (FA) molecules were located in the micelle shells and the PEG segments were in the outer corona, as confirmed by pyrene fluorescence probe techniques, transmission electron microscopy (TEM), dynamic lighting scattering (DLS), and dissipative particle dynamics (DPD) simulation. The folate-conjugated polyurethane micelles displayed enhanced drug loading capacity for doxorubicin (DOX), sustained drug release, preferential internalization by the human epidermoid carcinoma cell line (KB cells) and pronounced cytotoxicity compared to polyurethane micelles without FA, as verified by typical confocal microscopy images (CLSM) and methyl tetrazolium (MTT) assay, respectively. Our present work provides a new route for the preparation of folate-conjugated polyurethanes with high FA content, which could be a good candidate for active targeting conjugates for multifunctional carriers to achieve efficient drug delivery.
Co-reporter:Mingming Ding, Xin Zeng, Xueling He, Jiehua Li, Hong Tan, and Qiang Fu
Biomacromolecules 2014 Volume 15(Issue 8) pp:
Publication Date(Web):June 30, 2014
DOI:10.1021/bm500506v
A cell internalizable and intracellularly degradable micellar system, assembled from multiblock polyurethanes bearing cell-penetrating gemini quaternary ammonium pendent groups in the side chain and redox-responsive disulfide linkages throughout the backbone, was developed for potential magnetic resonance imaging (MRI) and drug delivery. The nanocarrier is featured as a typical “cleavable core–internalizable shell–protective corona” architecture, which exhibits small size, positive surface charge, high loading capacity, and reduction-triggered destabilization. Furthermore, it can rapidly enter tumor cells and release its cargo in response to an intracellular level of glutathione, resulting in enhanced drug efficacy in vitro. The magnetic micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles demonstrate excellent MRI contrast enhancement, with T2 relaxivity found to be affected by the morphology of SPIO-clustering inside the micelle core. The multifunctional carrier with good cytocompatibility and nontoxic degradation products can serve as a promising theranostic candidate for efficient intracellular delivery of anticancer drugs and real-time monitoring of therapeutic effect.
Co-reporter:Hong Tan, Zhigao Wang, Jiehua Li, Zhicheng Pan, Mingming Ding, and Qiang Fu
ACS Macro Letters 2013 Volume 2(Issue 2) pp:146
Publication Date(Web):January 25, 2013
DOI:10.1021/mz3005583
The shape of polymer micelles is important for pharmaceutical applications as drug delivery. In this article, an approach inducing sphere-to-rod transition of multiblock polyurethane micelles has been developed through introducing a second hydrophilic component phosphatidylcholine group into the polymer chains. Time-resolved dynamic light scattering (DLS), combined with transmission electron microscopy (TEM), was employed to investigate the kinetics of morphology transition. Moreover, a dissipative particle dynamics (DPD) simulation method was applied to study the mechanism of sphere-to-rod transition. These experimental and simulation studies revealed that the hydrophilic phosphatidylcholine groups can create defects on the surfaces of spherical polyurethane micelles, thus, making positive contribution to adhesive collisions and leading to the fusion of spherical micelles into rod-like micelles. This finding provides new insight into the origins of rod-like polymer micelles, which is valuable for the design and preparation of novel polymeric drug carriers with tailored properties.
Co-reporter:Jian Yang, Yunlong Gao, Jiehua Li, Mingming Ding, Feng Chen, Hong Tan and Qiang Fu
RSC Advances 2013 vol. 3(Issue 22) pp:8291-8297
Publication Date(Web):21 Mar 2013
DOI:10.1039/C3RA40515J
In this study, to obtain polycarbonate urethanes (PCU) with good mechanical properties and biostability, a series of polycarbonate urethanes containing various low levels of polydimethylsiloxane (PDMS) were synthesized via a two-step bulk polymerization using 4,4′-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BDO) as the hard segment, and PDMS–poly(1,6-hexyl carbonate) diol (PHC) mixed macrodiols as the soft segment, where the content of PDMS was limited to less than 30 wt%. The resulting polyurethanes were fully characterized using gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and mechanical tests. It was found that the incorporation of PDMS into the PCU enhanced the microphase separation and miscibility of PDMS with polar urethane hard segments. Moreover, these polyurethanes with higher molecular weights exhibit good mechanical properties, and are promising biostable polyurethane materials for long-term implant applications and interesting candidates for further investigation.
Co-reporter:Jiehua Li;Yi Zhang;Jian Yang;Jianshu Li ;Qiang Fu
Journal of Biomedical Materials Research Part A 2013 Volume 101A( Issue 5) pp:1362-1372
Publication Date(Web):
DOI:10.1002/jbm.a.34431
Abstract
To improve hemocompatibility of biomedical polyurethanes (PUs), a series of new fluorinated phospholipid end-capped polyurethanes (FPCPUs) as blending PU additives were designed and synthesized using diphenyl methane diisocyanate and 1,4-butanediol as hard segment, poly(tetramethylene glycol), polypropylene glycol, polycarbonate diols, and polyethylene glycol as soft segments, respectively, aminofunctionalized hybrid hydrocarbon/fluorocarbon double-chain phospholipid as end-capper. The bulk structures and surface properties of the obtained FPCPUs were fully characterized by 1H NMR, Fourier transform infrared, gel permeation chromatography, X-ray photoelectron spectroscopy, differential scanning calorimetry, atomic force microscopy, and water contact angle measurement. It was found that the phosphatidylcholine groups could enrich on the surfaces and subsurfaces with the help of the fluorocarbon chains and self-assemble into mimic biomembrane on these polymer surfaces. These surfaces could effectively suppress fibrinogen adsorption, as evaluated by enzyme-linked immunosorbent assay method. Our work indicates that the FPCPUs should be one of the most potential modified additives for enhancing hemocompatibility of traditional medical PUs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Co-reporter:Nijia Song, Mingming Ding, Zhicheng Pan, Jiehua Li, Lijuan Zhou, Hong Tan, and Qiang Fu
Biomacromolecules 2013 Volume 14(Issue 12) pp:
Publication Date(Web):November 12, 2013
DOI:10.1021/bm401342t
New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.
Co-reporter:Mingming Ding, Nijia Song, Xueling He, Jiehua Li, Lijuan Zhou, Hong Tan, Qiang Fu, and Qun Gu
ACS Nano 2013 Volume 7(Issue 3) pp:1918
Publication Date(Web):February 14, 2013
DOI:10.1021/nn4002769
Specific accumulation of therapeutics at tumor sites to improve in vivo biodistribution and therapeutic efficacy of anticancer drugs is a major challenge for cancer therapy. Herein, we demonstrate a new generation of intelligent nanosystem integrating multiple functionalities in a single carrier based on multifunctional multiblock polyurethane (MMPU). The smart nanocarriers equipped with stealth, active targeting, and internalizable properties can ferry paclitaxel selectively into tumor tissue, rapidly enter cancer cells, and controllably release their payload in response to an intracellular acidic environment, thus resulting in an improved biodistribution and excellent antitumor activity in vivo. Our work provides a facile and versatile approach for the design and fabrication of smart intracellular targeted nanovehicles for effective cancer treatment, and opens a new era in the development of biodegradable polyurethanes for next-generation nanodelivery systems.Keywords: biodegradable multifunctional multiblock polyurethane; cancer therapy; intelligent; intracellular drug delivery; nanomedicine; stimuli-responsive; target
Co-reporter:Ni-jia Song;Xia Jiang;Jie-hua Li;Yong Pang 庞勇
Chinese Journal of Polymer Science 2013 Volume 31( Issue 10) pp:1451-1462
Publication Date(Web):2013 October
DOI:10.1007/s10118-013-1315-7
To better investigate the degradation and biocompatibility of waterborne biodegradable polyurethanes for tissue engineering, a series of new waterborne biodegradable polyurethanes (PEGPUs) with low degree of crosslinking was synthesized using IPDI, BDO and L-lysine as hard segments, PCL and PEG as soft segment. The bulk structures and properties of the prepared polyurethanes were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), tensile mechanical tests and water contact angle (WCA) measurements. The degree of microphase separation was slightly improved because of the lowered crosslinking degree of these PEGPUs in comparison with the high cross-linking degree samples, leading to good mechanical properties, as indicated by DSC and stress-strain data. Moreover, biodegradability of the polyurethanes was evaluated in phosphate buffer solutions (PBS) under different pH values and enzymatic solution at pH 7.4 through weight loss monitoring. The results suggested that the degradation of these PEGPUs was closely related to their bulk and surface properties. And the degradation products didn’t show apparent inhibition effect against fibroblasts in vitro. These studies demonstrated that the waterborne biodegradable polyurethanes could find potential use in soft tissue engineering and tissue regeneration.
Co-reporter:Mingming Ding;Jiehua Li;Xueling He;Nijia Song;Yi Zhang;Lijuan Zhou;Qun Gu;Hua Deng;Qiang Fu
Advanced Materials 2012 Volume 24( Issue 27) pp:3639-3645
Publication Date(Web):
DOI:10.1002/adma.201200954
Co-reporter:Mingming Ding;Jiehua Li;Xueling He;Nijia Song;Yi Zhang;Lijuan Zhou;Qun Gu;Hua Deng;Qiang Fu
Advanced Materials 2012 Volume 24( Issue 27) pp:
Publication Date(Web):
DOI:10.1002/adma.201290165
Co-reporter:Mingming Ding, Jiehua Li, Hong Tan and Qiang Fu
Soft Matter 2012 vol. 8(Issue 20) pp:5414-5428
Publication Date(Web):01 Mar 2012
DOI:10.1039/C2SM07402H
The self-assembly of biodegradable polyurethanes constitutes an important area of research for the development of polymeric materials in biomedicine. In particular, colloidal polyurethane assemblies can increase the solubility and stability of hydrophobic compounds, and improve the specificity and efficiency of drug action. Their nanoscale size and modular functionality make them promising for the injectable, targeted and controlled delivery of various therapeutic agents and imaging probes into required cells. Additionally, cationic polyurethanes are able to self-assemble with nucleic acids into nanoparticles to enter cells for efficient gene transfection. These emerging nanocarriers open the door for addressing the failure of traditional localized delivery systems, and present a compelling future opportunity to achieve personalized therapy as versatile candidates. This review article highlights the research progress in the self-assembly of biodegradable polyurethanes for controlled delivery applications, with particular attention being paid to some representative vehicles such as self-assembled polyurethane micelles, nanogels, and polyurethane/DNA complexes, which have emerged as the focus of interest in recent years.
Co-reporter:Dongsheng Tan;Xiaoqing Zhang;Jiehua Li;Qiang Fu
Journal of Biomedical Materials Research Part A 2012 Volume 100A( Issue 2) pp:380-387
Publication Date(Web):
DOI:10.1002/jbm.a.33191
Abstract
In order to improve the blood compatibility, poly(ether urethane) (PEU) and fluorinated phosphorylcholine polyurethane (P-HFPC) were used to prepare PU/P-HFPC blends by solution mixing. The hemocompatibility in vitro was evaluated with protein adsorption and platelet-rich plasma (PRP) contact tests. It was found that the amount of adsorbed protein on surface was decreased by 87%, and almost no platelet adhesion and activation was observed on the surface of blends when P-HFPC content was above 5 wt %. After adding P-HFPC, the blends basically kept favorable mechanical properties of PEU though the content of P-HFPC rises to 20 wt %. To better understand the relationship between structure and properties, the phase structure and surface property of the blend films were further investigated via differential scanning calorimetry, dynamic mechanical analysis, atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle measurements. The results indicated that the fluorinated phosphorylcholine units could be easily enriched on the surface of blend films due to the phase separation between the PEU and P-HFPC. Therefore, ordinary poly(ether urethane)s can obtain both satisfactory blood compatibility and good mechanical properties just by blending with small amount of P-HFPC. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Co-reporter:Dongsheng Tan, Xiaoqing Zhang, Jiehua Li, Hong Tan, Qiang Fu
Applied Surface Science 2012 Volume 258(Issue 7) pp:2697-2706
Publication Date(Web):15 January 2012
DOI:10.1016/j.apsusc.2011.10.120
Abstract
A novel phospholipid containing double chains and phosphotidylcholine polar head groups, 2-(10-(2-aminoethylamino)-10-oxodecanamido)-3-(decyloxy)-3-oxopropyl phosphorylcholine (ADDPC), was synthesized and characterized. Two kinds of double-chain phospholipid end-capped polyurethanes with different soft segments were prepared. The structure of prepared polyurethanes was characterized by X-ray photoelectron spectroscopic (XPS), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectrometry and atomic force microscope (AFM), which indicated that the double-chain phospholipids enriched onto the top surface of the prepared polyurethane films. The preliminary evaluation of blood compatibility showed that these novel phospholipid end-capped polyurethanes could suppress platelet adhesion and activation effectively. This property did not depend on the chemical structure of polyurethanes. In addition, according to tensile test results, the phospholipid polyurethanes kept good mechanical properties in comparison with original polyurethanes. It is suggested that double-chain phospholipid end-caption has good potential for achieving both hemocompatibility and good mechanical properties simultaneously for polyurethanes.
Co-reporter:Peng-jun Wan;Dong-sheng Tan;Zheng-sheng Li
Chinese Journal of Polymer Science 2012 Volume 30( Issue 2) pp:190-198
Publication Date(Web):2012 March
DOI:10.1007/s10118-012-1111-9
To explore construction of novel mimicking biomembrane on biomaterials surfaces, a new polymerizable phosphatidylcholine containing a long monoalkyl chain ended with acryl group (AASOPC) was designed and synthesized, which was easily derived from the terminal amino group of 9-(2-amino-ethylcarbamoyl)-nonyl-1-phosphatidyl-choline (ASOPC) reacting with acryloyl chloride. The obtained AASOPC was grafted on poly(ethylene terephthalate) (PET) via surface-initiated atom-transfer radical polymerization (SI-ATRP) to form mimicking biomembrane. These modified surface structures of PET were investigated using water contact angle (WAC), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The results indicated that the new mimicking phosphatidylcholine biomembrane could be prepared on inert polymer surfaces by using the acryloyl phosphatidylcholine (AASOPC) via surface-initiated atom transfer radical polymerization (SI-ATRP).
Co-reporter:Lijuan Zhou, Dong Liang, Xueling He, Jiehua Li, Hong Tan, Jianshu Li, Qiang Fu, Qun Gu
Biomaterials 2012 33(9) pp: 2734-2745
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.11.009
Co-reporter:Mingming Ding, Zongzheng Qian, Jin Wang, Jiehua Li, Hong Tan, Qun Gu and Qiang Fu
Polymer Chemistry 2011 vol. 2(Issue 4) pp:885-891
Publication Date(Web):20 Jan 2011
DOI:10.1039/C0PY00376J
We have recently developed a new group of cationic biodegradable multiblock poly(ε-caprolactone urethane)s bearing gemini quaternary ammonium pendant groups and methoxyl-poly(ethylene glycol) (m-PEG) end chains. In this study, to endow polyurethane with attractive amphiphilicity and good biocompatibility, and to achieve a fundamental understanding on the structure-property relationship of these polyurethanes in favor of designing and preparing new generation of polyurethanes with more attractive amphiphilicity and better biocompatibility, varying amounts of m-PEG were introduced into the polyurethane chains and the effect of PEG content on the polymer bulk properties was investigated in detail by using Fourier transform infrared (FTIR) spectra, differential scanning calorimetry (DSC), water contact angle (WCA) measurements, polarizing light microscopy (PLM) and in vitrodegradation studies. It was found that the incorporation of PEG has direct effects on the phase behaviors, thermal properties, hydrophilicity and degradable ability of poly(ε-caprolactone urethane)s. Moreover, these polyurethanes exhibit good cytocompatibility, which are promising biodegradable carrier materials in drug delivery and interesting candidates for further study.
Co-reporter:Zhigao Wang, Lunquan Yu, Mingming Ding, Hong Tan, Jiehua Li and Qiang Fu
Polymer Chemistry 2011 vol. 2(Issue 3) pp:601-607
Publication Date(Web):04 Nov 2010
DOI:10.1039/C0PY00235F
To obtain rapid biodegradable biomaterials, a biodegradable triblock oligomer poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) was designed and synthesized as a soft segment of polyurethane. Then new nontoxic biodegradable polyurethanes were prepared using the same stoichiometric ratio of PLA-PEG-PLA, L-lysine ethyl ester diisocyanate (LDI), and 1,4-butanediol (BDO). The molecular weights of polyurethanes were controlled by adjusting the polymerization temperature. The resulting polyurethanes were characterized by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Furthermore, the biodegradability of the synthesized polyurethanes was evaluated at 37 °C in phosphate buffer solutions (PBS) under different pH values and enzymatic solution at pH 7.4. The results showed that these polyurethanes could be rapidly degraded in PBS and enzymatic solution, as demonstrated by weight loss measurements and scanning electron microscope (SEM) observations. The degradation rates of these polyurethanes were mainly regulated by microphase separation degree, and could be restrained in lower pH value PBS. Moreover, the degradation products did not significantly decrease the pH value of incubation media, which would be useful to improve biocompatibilities of these polyurethanes in vivo. The current work provides a more promising approach to prepare nontoxic biodegradable polyurethanes with rapid degradation rates. These new materials may find potential use for drug delivery systems and magnetic resonance imaging (MRI) contrast agents.
Co-reporter:Lunquan Yu, Lijuan Zhou, Mingming Ding, Jiehua Li, Hong Tan, Qiang Fu, Xueling He
Journal of Colloid and Interface Science 2011 Volume 358(Issue 2) pp:376-383
Publication Date(Web):15 June 2011
DOI:10.1016/j.jcis.2011.03.007
In order to obtain targeting polyurethane micelle drug carriers, a series of biodegradable folate conjugated polyurethanes (FPUs) were synthesized using poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) as soft segments, l-lysine ethyl ester diisocyanate (LDI) and 1,3-propanediol (PDO) as hard segments, and folic acid–ethylenediamine conjugate (FA–EDA) as an end-capping reagent. The resultant FPUs were fully characterized by 1H NMR, Fourier-transform infrared (FTIR) spectroscopy, ultraviolet spectrophotometry (UV), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). These polymers can self-assemble into micelles in aqueous solutions confirmed by dynamic light scattering (DLS), pyrene fluorescence probe techniques, and transmission electron microscopy (TEM). The results indicated that the bulk structures and micellar properties of the prepared polyurethanes could be controlled by varying the PEG content in the soft segments. The present work provides a facile approach to prepare amphiphilic multiblock copolymers with tumor targeting moiety, which is a good candidate as biodegradable carriers for active intracellular drug delivery.Graphical abstractMicellar properties of folate conjugated polyurethane (FPU) could be controlled by varying the PEG content in the soft segments, which makes FPU a possible carrier for active intracellular drug delivery.Highlights► A novel folate conjugated polyurethane (FPU) has been synthesized using PEG, PCL, and LDI. ► Micellar properties of the FPUs could be controlled by varying the PEG content in the soft segments. ► Our work provides a facile avenue to prepare amphiphilic copolymers with tumor targeting moieties.
Co-reporter:Dong-sheng Tan;Xiao-qing Zhang;Jian-chuan Wang
Chinese Journal of Polymer Science 2011 Volume 29( Issue 5) pp:615-626
Publication Date(Web):2011 September
DOI:10.1007/s10118-011-1071-5
A series of fluorinated phosphatidylcholine polyurethane macromolecular additives were synthesized by solution polymerization using methylenebis(phylene isocyanates) (MDI) and 1,4-butanediol (BDO) as hard segments, a new phoshporycholine, 2-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluoro-10-(2-hydroxyethoxy)decyloxy) ethyl phosphorycholine (HDFOPC) as end-capper, and four polydiols, poly(tetramethylene glycol)s (PTMG), polydimethylsiloxane (PDMS), poly(1,6-hexyl-1,5-pentylcarbonate) (PHPC) and poly(propylene glycol) (PPG) as soft segments, respectively. The chemical structures of the synthesized polyurethanes were characterized by 1H-NMR and FTIR. DSC and DMA were employed to study the phase behavior of these novel polyurethanes due to their great influences on the surface properties, and hence their interactions with bio-systems. The results showed that phase separation of the fluorinated phosphatidylcholine end-capped polyurethanes was increased in comparison with that of normal polyurethanes. The effect of fluorinated phosphatidylcholine end-capped groups on the phase behavior was further demonstrated by analyzing the degree of hydrogen-bonding between hard and soft segments.
Co-reporter:Mingming Ding, Xueling He, Zhigao Wang, Jiehua Li, Hong Tan, Hua Deng, Qiang Fu, Qun Gu
Biomaterials 2011 32(35) pp: 9515-9524
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.08.074
Co-reporter:Lijuan Zhou, Lunquan Yu, Mingming Ding, Jiehua Li, Hong Tan, Zhigao Wang, and Qiang Fu
Macromolecules 2011 Volume 44(Issue 4) pp:857-864
Publication Date(Web):January 19, 2011
DOI:10.1021/ma102346a
To obtain a pH-sensitive multifunctional polyurethane micelle drug carrier, a novel pH-sensitive macrodiol containing acid-cleavable hydrazone linkers, poly(ε-caprolactone)−hydrazone−poly(ethylene glycol)−hydrazone−poly(ε-caprolactone) diol (PCL−Hyd−PEG−Hyd−PCL), was synthesized and characterized with proton nuclear magnetic resonance spectra (1H NMR). A series of pH-sensitive biodegradable polyurethanes (pHPUs) were designed and synthesized using pH-sensitive macrodiol, l-lysine ethyl ester diisocyanate (LDI) and l-lysine derivative tripeptide as chain extender, which can provide an active reaction site for the development of positive target polyurethane micelles for drug delivery. The bulk structures of the prepared polyurethanes were carefully characterized with 1H NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The polyurethanes could be cleaved in acidic media (pH ∼ 4−6) as well as degraded in PBS and enzymatic solution, as demonstrated by 1H NMR and weight loss, respectively. The cytotoxicity of their degradation products was evaluated using methylthiazoletetrazolium (MTT) assay in vitro, resulting in no apparent inhibition effect on the fibroblasts. These polyurethanes could self-assemble into micelles in aqueous solutions, as verified using dynamic light-scattering (DLS). Our present work provides a new method for the preparation of amphiphilic multiblock polyurethanes with pH-sensitivity and biodegradability. It could be a good candidate as biodegradable multifunctional carrier for active intracellular drug delivery.
Co-reporter:Jiehua Li, Yezhong Chen, Zhigao Wang, Mingming Ding, Hong Tan, Qiang Fu, and Xia Jiang
Langmuir 2011 Volume 27(Issue 17) pp:10859-10866
Publication Date(Web):June 20, 2011
DOI:10.1021/la201610w
In this article, we designed and synthesized an amino-functionalized hybrid hydrocarbon/fluorocarbon double-chain phospholipid (ACFPC) containing one chain with the hydrophobic fluorocarbon chain and terminal amino, amide, and ether linkages and one chain with the hydrocarbon chain. The novel reactive phospholipid was fully characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). Then the self-assembly behaviors of the hybrid double-chain phospholipid in aqueous and acidic media were investigated with transmission electron microscopy (TEM), the critical micelle concentration (cmc), dynamic light scattering (DLS), and the hydrocarbon double-chain phospholipid (ACCPC) for comparison. Moreover, their self-assembled structures in aqueous and acidic media were simulated using the dissipative particle dynamics (DPD) method. These results suggest that the fluorocarbon/hydrocarbon hybrid-chain phospholipid can self-assemble into a more stable microstructure compared to the double hydrocarbon chain phospholipid, which will have the potential ability to self-assemble into a more stable minicking biomembrane structure onto material surfaces to inhibit protein adsorption under complicated physiological conditions.
Co-reporter:Xia Jiang;Kunjie Wang;Mingming Ding
Journal of Materials Science: Materials in Medicine 2011 Volume 22( Issue 4) pp:819-827
Publication Date(Web):2011 April
DOI:10.1007/s10856-011-4265-z
Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) peptide has frequently been used in the biomedical materials to enhance adhesion and proliferation of cells. In this work, we modified the nontoxic biodegradable waterborne polyurethanes (WBPU) with GRGDSP peptide and fabricated 3-D porous scaffold with the modified WBPU to investigate the effect of the immobilized GRGDSP peptide on human umbilical vein endothelial cells (HUVECs) adhesion and proliferation. A facile and reliable approach was first developed to quantitative grafting of GRGDSP onto the WBPU molecular backbone using ethylene glycol diglycidyl ether (EX810) as a connector. Then 3-D porous WBPU scaffolds with various GRGDSP content were fabricated by freeze-drying the emulsion. In both of the HUVECs adhesion and proliferation tests, enhanced cell performance was observed on the GRGDSP grafted scaffolds compared with the unmodified scaffolds and the tissue culture plate (TCP). The adhesion rate and proliferation rate increased with the increase of GRGDSP content in the scaffold and reached a maximum with peptide concentration of 0.85 μmol/g based on the weight of the polyurethanes. These results illustrate the necessity of the effective control of the GRGDSP content in the modified WBPU and support the potential utility of these 3-D porous modified WBPU scaffolds in the soft tissue engineering to guide cell adhesion, proliferation and tissue regeneration.
Co-reporter:Mingming Ding, Lijuan Zhou, Xiaoting Fu, Hong Tan, Jiehua Li and Qiang Fu
Soft Matter 2010 vol. 6(Issue 9) pp:2087-2092
Publication Date(Web):31 Mar 2010
DOI:10.1039/B926689E
Unique self-assembly behavior of novel nontoxic gemini cationic biodegradable multiblock poly(ε-caprolactone urethane)s which contain both gemini quaternary ammonium and PEG groups is firstly reported. The micellar size, size distributions, zeta potential, CMC and Kv could be well-tailored for application in drug and gene delivery.
Co-reporter:Jiehua Li, Dongsheng Tan, Xiaoqing Zhang, Hong Tan, Mingming Ding, Changxiu Wan, Qiang Fu
Colloids and Surfaces B: Biointerfaces 2010 Volume 78(Issue 2) pp:343-350
Publication Date(Web):1 July 2010
DOI:10.1016/j.colsurfb.2010.03.027
In this study, a surface grafting of nonfouling poly(ethylene glycol) methyl ether acrylate (PEGMA) on poly(ethylene terephthalate) (PET) was carried out via surface-initiated atom-transfer radical polymerization (SI-ATRP) to improve hemocompatibility of polymer based biomaterials. To do this, the coupling agent with hydroxyl groups for the ATRP initiator was first anchored on the surface of PET films using photochemical method, and then these hydroxyl groups were esterified by bromoisobutyryl bromide, from which PET with various main chain lengths of PEGMA was prepared. The structures and properties of modified PET surfaces were investigated using water contact angle (WAC), ATR-FTIR, X-ray photoelectron spectroscopy (XPS) and Atomic force microscopy (AFM). The molecular weights of the free polymer from solution were determined by gel permeation chromatography (GPC). These results indicated that grafting of PEGMA on PET film is a simple way to change its surface properties. The protein adsorption resistance on the surfaces of PET was primarily evaluated by an enzyme-linked immunosorbent assay (ELISA). The result demonstrated that the protein adsorption could be well suppressed by poly(PEGMA) brush structure on the surface of PET. This work provides a new approach for polymers to enhance their biocompatibility.
Co-reporter:Mingming Ding, Jiehua Li, Xiaoting Fu, Jian Zhou, Hong Tan, Qun Gu and Qiang Fu
Biomacromolecules 2009 Volume 10(Issue 10) pp:
Publication Date(Web):September 28, 2009
DOI:10.1021/bm9006826
Novel cationic biodegradable multiblock poly(ε-caprolactone urethane)s that contain gemini quaternary ammonium side groups on the hard segments were developed. To obtain these polyurethanes, a new l-lysine-derivatized diamine containing gemini quaternary ammonium side groups (GA8) was first synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectra (NMR), mass spectrometry (MS), and high-resolution mass spectra (HRMS). Then a series of gemini poly(ε-caprolactone urethane)s were designed and prepared using l-lysine ethyl ester diisocyanate (LDI), poly(ε-caprolactone) (PCL) diols, 1,4-butandiol (BDO), and GA8 and were terminated by methoxyl-poly(ethylene glycol) (m-PEG). The obtained polyurethanes were fully characterized by 1H NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC), FTIR, and water contact angle (WCA) measurement. The gemini polyurethane shows a rapid rate of hydrolytic and enzymatic degradation, as demonstrated by weight loss and polarizing light microscopy (PLM) observations. In vitro cytotoxicity analysis suggests that both the polyurethanes and their degradation products do not show significant inhibition effect against fibroblasts. Our work provides a new way to synthesize nontoxic and amphiphilic multiblock polyurethanes with rapid degradation rate, and these new materials could be good candidates as biodegradable carriers for drug and gene delivery.
Co-reporter:Yi Zhang, Wei He, Jiehua Li, Kunjie Wang, Jianshu Li, Hong Tan and Qiang Fu
Inorganic Chemistry Frontiers 2017 - vol. 1(Issue 2) pp:NaN368-368
Publication Date(Web):2016/08/15
DOI:10.1039/C6QM00039H
In this study, a series of waterborne biodegradable polyurethanes with antibacterial and biocompatible properties were developed. To obtain these polyurethanes, lysine-derivative gemini quaternary ammonium salt (GQAS) chain extenders with different hydrophobic alkyl chain lengths (named EGn, where n = 8, 12, 16; the hydrophobic alkyl chain length of GQAS) were designed and synthesized. Then, waterborne biodegradable polyurethanes (PCLPUn) were prepared using isophorone diisocyanate (IPDI), poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), L-lysine and EGn. The antibacterial activities of these EGn and PCLPUn emulsions were evaluated by a minimal inhibitory concentration (MIC) method, and the antibacterial and antifouling functionalities of the PCLPUn film surfaces were confirmed by a contact-active antibacterial and culture-based method using both Gram-positive and Gram-negative bacteria. The in vitro degradation and cytotoxicity of these obtained polyurethanes were also systematically investigated. These results indicated that the PCLPUn films possessed good antibacterial and antifouling abilities, biodegradability, and good biocompatibility. Notably, PCLPU12 shows the best antibacterial activity and cytocompatibility. Such antibacterial materials could be degraded to non-toxic components, and potentially be widely used in medical and environmental applications, especially as biodegradable coatings of surgical equipment and medical implants.
Co-reporter:Dongsheng Tan, Zhen Li, Xuelin Yao, Chunlan Xiang, Hong Tan and Qiang Fu
Journal of Materials Chemistry A 2014 - vol. 2(Issue 10) pp:NaN1353-1353
Publication Date(Web):2013/12/03
DOI:10.1039/C3TB21473G
To study the influence of fluorinated surfaces and biomimetic surfaces on the improvement of the blood compatibility of polymers, three monomers containing a fluorinated tail and/or phosphorylcholine groups were designed and synthesized, and were then introduced into polyurethanes based on 4,4′-diphenylmethane diisocyanate (MDI), poly(tetramethylene glycol) (PTMG) and 1,4-butanediol (BDO) via end-capping. The bulk and surface characterization of the polyurethanes was carried out by dynamic mechanical analysis (DMA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopic analysis (XPS), atomic force microscope (AFM), and water contact angle measurements. The results indicate that the fluorocarbon chains can drive the phosphorylcholine groups to aggregate at the surface of polyurethane, and the two components show spontaneous arrangement to adapt to the environment when in contact with water. The preliminary evaluation of hemocompatibility was carried out via fibrinogen adsorption and platelet adhesion. The fluorocarbon chains and phosphorylcholine groups showed a synergistic effect on the improvement of hemocompatibility.
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![(3r,4r,5s,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-one](http://img.cochemist.com/ccimg/6000/5965-65-1_b.png)
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![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4_b.png)
