Co-reporter:Yu Qin;Changyu Wang;Yun Jiang;Tao Liu;Jianyong Yang;Run Lin
RSC Advances (2011-Present) 2017 vol. 7(Issue 66) pp:41675-41685
Publication Date(Web):2017/08/23
DOI:10.1039/C7RA08287H
A novel phosphorylcholine oligomer-grafted and folate moiety-labeled graphene oxide (GO–PCn–FA) was designed, prepared, and characterized by Fourier transform infrared spectra, nuclear magnetic resonance, Raman spectra, X-ray diffraction, X-ray photoelectron spectroscopy, scanning transmission electron microscopy, transmission electron microscopy, and atomic force microscopy. GO–PCn–FA proved to be an excellent water-soluble and pH-responsive drug carrier for the targeted delivery of doxorubicin (DOX) with a drug loading content of 21%. An in vitro cytotoxicity assay and flow cytometry analysis revealed the superior biocompatibility of GO–PCn–FA compared to normal cells, while DOX-loaded GO–PCn–FA exerted efficient eradication of tumor cells, especially of those with folate receptor expression. An in vivo test showed that GO–PCn–FA was deposited mainly in the pulmonary parenchyma after intravenous administration, and no obvious adverse effect was observed. In summary, phosphorylcholine oligomer-grafted graphene oxide was developed for targeted drug delivery with optimal biocompatibility.
Co-reporter:Yu Liu, Han Zhong, Yu Qin, Yan Zhang, Xinfeng Liu and Tao Zhang
RSC Advances 2016 vol. 6(Issue 36) pp:30184-30193
Publication Date(Web):17 Mar 2016
DOI:10.1039/C6RA04349F
Graphene oxide (GO) and reduced graphene oxide (RGO) are attractive materials due to their potential biomedical applications, especially as drug delivery vehicles because of their huge specific surface area. In the current study, GO and RGO were prepared. In addition, a perylene derivative, phosphorylcholine oligomer grafted perylene (Perylene-PCn), was synthesized following the atom transfer radical polymerization procedure. In order to determine their structures, the products were characterized carefully with Fourier transform infrared spectra, proton nuclear magnetic resonance, X-ray photoelectron spectroscopy, wide angle X-ray diffraction, thermogravimetric analysis, and atomic force microscopy etc. The properties including fluorescence and biocompatibility were also evaluated. Utilizing the π–π stacking interaction of RGO and the perylene moiety, water dispersible RGO/Perylene-PCn composites were fabricated and then investigated as a vehicle for anti-tumor paclitaxel (PTX). The anti-tumor effects of free PTX and PTX@RGO/Perylene-PCn were compared with an in vitro cytotoxicity assay. The results demonstrated that RGO/Perylene-PCn can be used as an anti-tumor agent delivery vehicle for potential oncology applications.
Co-reporter:Fei Wang, Yan Zhang, Xiumian Chen, Bing Leng, Xin Guo, Tao Zhang
Colloids and Surfaces B: Biointerfaces 2016 Volume 143() pp:390-398
Publication Date(Web):1 July 2016
DOI:10.1016/j.colsurfb.2016.03.063
•Successful ALD mediated heparin immobilization on nitinol surface.•Al2O3 layer is beneficial to the grafting of biomolecules on metallic surface.•Improved hemocompatibility of nitinol surface.•Potential manufacture technology of functional carotid stents.Carotid-artery atherosclerosis is a common cause of ischemic stroke. Carotid-artery stenting (CAS) is one of the most effective treatments. However, In-stent restenosis (ISR) and re-endothelialization delay are two major issues of intravascular stent which affect clinical safety and reduce effects. In this study, atomic layer deposition (ALD) technology was applied to deposit a layer (10 nm) of Al2O3 on Nitinol surface as an intermediate functional layer. The alumina covered surface was then modified with a coupling agent 3-aminopropyltriethoxysilane (APS) and heparin sequentially in order to improve the hemocompatibility of Nitinol stents. The successful graft of APS and heparin onto Nitinol was proven by X-ray photoelectron spectroscopy. Furthermore, the predicted improvement in the biocompatibilities of modified Nitinol was confirmed by water contact angle measurement, protein adsorption, platelet adhesion, and plasma recalcification time determination. The results of hemolysis assay, cell proliferation and cytotoxicity tests revealed that the grafting of heparin on NiTi kept the original positive performance of nitinol material. The results indicate that ALD technology is of great potential for the manufacture of medical devices, especially for surface modifications and functionalization. ALD technology can help with modifications of inert metallic surfaces and therefore benefit implantable medical devices, especially intravascular stents.
Co-reporter:Qi Zhong;Qunlong Mao;Jin Yan;Wenming Liu;Jianguo Liu
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2015 Volume 103( Issue 3) pp:691-699
Publication Date(Web):
DOI:10.1002/jbm.b.33250
Abstract
Monitoring erosion progress of biodegradable drug carrying polymer coated on coronary drug eluting stents (DES) is largely hindered because of the small amount of coating material as well as the irregular profile of coating, both of which make the monitoring using traditional methods highly challenging. In our study, electrochemical impedance spectroscopy (EIS), a widely used method in the study of metal corrosion, was used to address the challenges traditional methods face. In vitro, remained mass and molecular weight drop data of film-like poly(lactide-co-glycolide) (PLGA) samples due to degradation were monitored using traditional mass loss measurement and size exclusion chromatography (SEC) methods. The obtained data were compared to the changes of capacitance and impedance measured by EIS from PLGA-coated stainless slices with an equivalent electrical circuit model. The results showed that the changes of the resistance and capacitance obtained by EIS, which indicates transformations of PLGA coating, can be correlated to the degradation measured by traditional methods, such as SEC. Furthermore, EIS method was applied to monitor and evaluate the erosion progress of a real stent with PLGA coating. Our results suggested that EIS method can accurately monitor real-time erosion process of thin polymer coatings on DES in situ. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 691–699, 2015.
Co-reporter:Huiyu Wang, Guofeng Yue, Chaoqun Dong, Fenglei Wu, Jia Wei, Yang Yang, Zhengyun Zou, Lifeng Wang, Xiaoping Qian, Tao Zhang, and Baorui Liu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 6) pp:4550
Publication Date(Web):February 26, 2014
DOI:10.1021/am500394j
Conventional in vitro circulating tumor cell (CTC) detection methods are always limited by blood sample volume because of the requirement of a large amount of blood. The aim of this study was to overcome the limitation by designing and making an in vivo CTC capture device. In this study, we designed and prepared a kind of proper material to serve the purpose of intervention. A method employing 3-aminopropyltriethoxysilane (γ-APS) as the coupling reagent to graft carboxybetaine methacrylate (CBMA) and to immobilize an anti-epithelial cell adhesion molecular (EpCAM) antibody on Nylon was developed. The results of X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy proved the successful graft of γ-APS and CBMA to Nylon. Furthermore, the predicted improvement in the biocompatibilities of our modified Nylon was confirmed by water contact angle measurement, bovine serum albumin adhesion, platelet adhesion, plasma recalcification time determination, and cytotoxicity tests. The tumor cells adhesion experiment revealed that Nylon with the antibody immobilized on it had an affinity for EpCAM positive tumor cells higher than that of pristine Nylon. Additionally, the capture ability of the CTCs was demonstrated in a nude mouse tumor model using the interventional device made of the modified Nylon wire. The positive results suggest that CBMA-grafted and anti-EpCAM antibody-immobilized Nylon is a promising new material for in vivo CTC capture devices.Keywords: carboxybetaine methacrylate; circulating tumor cells; interventional device; Nylon; surface modification;
Co-reporter:Yu Liu, Yan Zhang, Tao Zhang, Yongjun Jiang, Xinfeng Liu
Carbon 2014 Volume 71() pp:166-175
Publication Date(Web):May 2014
DOI:10.1016/j.carbon.2014.01.025
Using a random polymerization process on graphene oxide (GO), graphene oxide grafted with oligomers containing phosphorylcholine moieties (GO-PCn) was synthesized. The synthesis products were characterized by atomic force microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis and X-ray diffraction. The results revealed that the synthesized GO-PCn possessed greatly improved water solubility and remained stable in cell culture medium for several months. To evaluate the cytotoxicity of the GO-PCn, three cell lines (human umbilical vein endothelial cells, 264.7 murine macrophages and L929 murine fibroblasts) were cultured in different concentrations of GO and GO-PCn. GO-PCn demonstrated improved biocompatibility with all three cell lines. To investigate the mechanism of cellular uptake of the GO-PCn, fluorescein isothiocyanate-labeled GO-PCn was prepared. The results indicated that GO-PCn was incorporated by each cell type through endocytosis—a consequence of its near-micrometer size—and that it had no significant cytotoxicity.
Co-reporter:Chaoqun Dong, Huiyu Wang, Zhuo Zhang, Tao Zhang, Baorui Liu
Journal of Colloid and Interface Science 2014 Volume 432() pp:135-143
Publication Date(Web):15 October 2014
DOI:10.1016/j.jcis.2014.07.003
•CBMA oligomers were grafted from nylon surface with ATRP approaches.•The modification was found beneficial to blood compatibility of nylon.•EpCAM antibodies were immobilized on CBMA oligomers grafted nylon surface.•SGC7901 tumor cells were selectively captured from blood.Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices.
Co-reporter:Qi Zhong, Jin Yan, Xu Qian, Tao Zhang, Zhuo Zhang, Aidong Li
Colloids and Surfaces B: Biointerfaces 2014 Volume 121() pp:238-247
Publication Date(Web):1 September 2014
DOI:10.1016/j.colsurfb.2014.06.022
•Atomic layer deposition (ALD) was introduced into bio-interface fabrication.•Ultra-thin (10 nm) layer of Al2O3 was found to be beneficial to grafting of biomolecules.•Mimetic cell membrane surface was simply fabricated by grafting of phosphorylcholine moiety mediated with Al2O3 layer.•The modified surface is beneficial to blood compatibility and endothelial cells proliferation, thus conducive to intravascular stents.In-stent restenosis (ISR) and re-endothelialization delay are two major issues of intravascular stent in terms of clinical safety and effects. Construction of mimetic cell membrane surface on stents using phosphorylcholine have been regarded as one of the most powerful strategies to resolve these two issues and improve the performance of stents. In this study, atomic layer deposition (ALD) technology, which is widely used in semiconductor industry, was utilized to fabricate ultra-thin layer (10 nm) of alumina (Al2O3) on 316L stainless steel (SS), then the alumina covered surface was modified with 3-aminopropyltriethoxysilane (APS) and 2-methacryloyloxyethyl phosphorylcholine (MPC) sequentially in order to produce phosphorylcholine mimetic cell membrane surface. The pristine and modified surfaces were characterized using X-ray photoelectron spectroscopy, atomic force microscope and water contact angle measurement. Furthermore, the abilities of protein adsorption, platelet adhesion and cell proliferation on the surfaces were investigated. It was found that alumina layer can significantly enhance the surface grafting of APS and MPC on SS; and in turn efficiently inhibit protein adsorption and platelet adhesion, and promote the attachment and proliferation of human umbilical vein endothelial cells (HUVEC) on the surfaces. In association with the fact that the deposition of alumina layer is also beneficial to the improvement of adhesion and integrity of drug-carrying polymer coating on drug eluting stents, we expect that ALD technology can largely assist in the modifications on inert metallic surfaces and benefit implantable medical devices, especially intravascular stents.
Co-reporter:Tao Zhang;Meiyu Pan;Ji Dai;Zhexian Song;Ling He;Zhengsheng Jiang
Journal of Applied Polymer Science 2009 Volume 114( Issue 1) pp:107-115
Publication Date(Web):
DOI:10.1002/app.30475
Abstract
Manufacturing biomedical flexible Poly (vinyl chloride) (PVC) products requires the nontoxic plasticizers and the biocompatibility. In this study, a series of methoxylated poly(ethylene glycol)-poly(ε-caprolactone) diblock copolymer (MPEG-PCL) with variety molecule weight were synthesized by ring-opening polymerization of ε-caprolactone with methoxylated poly(ethylene glycol) (MPEG) as macroinitiator. The structure of the block copolymers was characterized utilizing FTIR, NMR, SEC, and DSC. Because the compatibility between PVC and PCL, a series of MPEG-PCL/PVC blends were prepared. The results of DSC and mechanical properties of blends show that PVC could be plasticized with MPEG-PCL and the diblock copolymer is probably to be used as a polymeric plasticizer for PVC. Moreover, the water contact angle results indicated that MPEG-PCL also provided PVC the hydrophilic properties. At the same time, it was found that the blends showed favorable anticoagulation property which can probably exploit the potential application of the blends in the biomedical areas. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Co-reporter:Tao Zhang, Min Xu, Ling He, Kai Xi, Min Gu, Zhengsheng Jiang
Carbon 2008 Volume 46(Issue 13) pp:1782-1791
Publication Date(Web):November 2008
DOI:10.1016/j.carbon.2008.07.033
Carbon nanotubes (CNTs) were rendered water-soluble by grafting on phosphoryl choline (PC). The modified CNTs were characterized utilizing Fourier transform infrared spectra, X-ray photoelectron spectra, thermogravimetric analysis, nuclear magnetic resonance, transmission electron microscopy, ultraviolet/visible absorbance spectra and dynamic laser light-scattering. The results show that the target products are easily dispersed in water and remain dispersed for at least three months. This study showed that both CNTs and CNT-PC induce no cytotoxicity on clonal pheochromocytoma cells (PC12) and human colon carcinoma cell lines (Caco-2). The grafted PC group confers water solubility and keeps the cell-compatibility of CNTs.
Co-reporter:Tao Zhang, Kai Xi, Min Gu, Zheng Sheng Jiang
Chinese Chemical Letters 2008 Volume 19(Issue 1) pp:105-109
Publication Date(Web):January 2008
DOI:10.1016/j.cclet.2007.10.002
Water-soluble property is the precondition of biomedical evaluation and application of carbon nanotube (CNT). Novel water-soluble CNT was synthesized in this letter by grafting phosphoryl choline (PC) onto multi-wall CNTs. Utilizing FTIR, XPS, TGA and TEM, the title CNTs were characterized and it was found that the target products could facilely dissolve in water.
Co-reporter:Ting Zhang, Meng Tang, Lu Kong, Han Li, Tao Zhang, Yuying Xue, Yuepu Pu
Journal of Hazardous Materials (2 March 2015) Volume 284() pp:73-82
Publication Date(Web):2 March 2015
DOI:10.1016/j.jhazmat.2014.11.013
•The cytotoxicity of three different MWCNTs was investigated.•Oxidative stress and inflammation were increased by raw MWCNTs and MWCNTs–COOH.•The physicochemical properties of MWCNTs lead to an increased bioactivity.•The mechanism of toxicity may involve the activation of the MAPK and NF-κB pathways.Carbon nanotubes (CNTs) are widely used in industry and biomedicine. While several studies have focused on biological matters, attempts to systematically elucidate the toxicity mechanisms of CNTs are limited. The aim of the present study was to evaluate and compare the cytotoxicity of raw multi-walled carbon nanotubes (MWCNTs) and MWCNTs functionalized with carboxylation (MWCNTs–COOH) or polyethylene glycol (MWCNTs–PEG) in murine macrophages. Our results show that only MWCNTs–COOH and raw MWCNTs alter the oxidative potential of macrophages by increasing reactive oxygen species and the expression of pro-inflammatory factors in both a concentration- and surface coating-dependent manner. The data suggest that compare with raw MWCNTs and MWCNTs–PEG, the MWCNTs–COOH produces a significant increase in ROS generation, interruption of ATP synthesis, and activation of the MAPK and NF-κB signaling pathways, which in turn upregulates IL-1β, IL-6, TNF-α, and iNOS to trigger cell death. These findings suggest that contributory cellar uptake caused by physicochemical factors rather than residual metal catalysts plays a role in ROS-mediated pro-inflammatory responses in vitro.