Co-reporter:Lei Zhang, Yi Wang, Xiaobin Zhang, Xiao Wei, Xiang Xiong, and Shaobing Zhou
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 4) pp:
Publication Date(Web):January 10, 2017
DOI:10.1021/acsami.6b14078
Highly effective delivery of therapeutic agents into target cells using nanocarriers and subsequently rapid intracellular release are of great importance in cancer treatment. Here, we developed an enzyme and redox dual-responsive polymeric micelle with active targeting abilities to achieve rapid intracellular drug release. To overcome both its poor solubility in water and instability in the blood circulation, camptothecin (CPT) was chemically conjugated to monomethyl poly(ethylene glycol) (mPEG) via a redox-responsive linker to form polymeric prodrugs. The enzyme-responsive function is achieved by connecting hydrophobic polycaprolactone segments and hydrophilic PEG segments with azo bonds. Additionally, the end of the PEG segment was decorated with phenylboronic acid (PBA), endowing the nanocarriers with active targeting abilities. The dual-responsive targeting polymeric micelles can be generated by self-assembly of a mixture of the polymeric prodrug and enzyme-responsive copolymer. The in vitro drug release profile revealed that CPT was rapidly released from the micelles under a simulated condition similar to the tumor cell microenvironment. In vivo and ex vivo fluorescence imaging indicated that these micelles possess excellent specificity to target hepatoma carcinoma cells. The antitumor effect in mice liver cancer cells (H22) in tumor-bearing Kunming (KM) mice demonstrated that this nanocarrier exhibits high therapeutic efficiency in artificial solid tumors and low toxicity to normal tissues, with a survival rate of approximately 100% after 160 days of treatment.Keywords: active-targeting; enzyme-responsive; intracellular release; nanocarrier; redox-responsive;
Co-reporter:Yi Wang, Lei Zhang, Xiaobin Zhang, Xiao Wei, Zhaomin Tang, and Shaobing Zhou
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 9) pp:5833
Publication Date(Web):February 18, 2016
DOI:10.1021/acsami.5b11569
The importance of achieving a high content of responsive groups of drug carriers is well-known for achieving rapid intracellular drug release; however, very little research has been published on this subject. Here, we present an entirely new strategy to synthesize a highly reduction-sensitive polymer-drug conjugate with one disulfide bond corresponding to each resultant copolymer through a precise ring-opening polymerization of ε-caprolactone that is initiated by a monoprotected cystamine. Simultaneously, the anticancer drug doxorubicin is chemically conjugated to the polymer via pH-responsive hydrazone bonds, which effectively prevent premature drug release in the blood circulation. The 3-aminophenylboronic acid (PBA) targeting ligands endow an active-targeting ability that significantly prompts the specific internalization of nanocarriers by tumor cells and thus results in excellent cytotoxicity against tumor cells. The concept of precise polymerization is put forward to achieve multifunctional nanocarriers for the first time. This study is expected to inspire the development of a highly environment-responsive nanoplatform for drug delivery in future clinical applications.Keywords: cancer therapy; nanoplatform; precise polymerization; reduction-responsive; ultrasensitive
Co-reporter:Guang Yang, Jie Wang, Yi Wang, Long Li, Xing Guo, and Shaobing Zhou
ACS Nano 2015 Volume 9(Issue 2) pp:1161
Publication Date(Web):January 20, 2015
DOI:10.1021/nn504573u
Nanocarriers have attracted broad attention in cancer therapy because of their ability to carry drugs preferentially into cancer tissue, but their application is still limited due to the systemic toxicity and low delivery efficacy of intravenously delivered chemotherapeutics. In this study, we develop a localized drug delivery device with combination of an active-targeting micellar system and implantable polymeric nanofibers. This device is achieved first by the formation of hydrophobic doxorubicin (Dox)-encapsulated active-targeting micelles assembled from a folate-conjugated PCL–PEG copolymer. Then, fabrication of the core–shell polymeric nanofibers is achieved with coaxial electrospinning in which the core region consists of a mixture of poly(vinyl alcohol) and the micelles and the outer shell layer consists of cross-linked gelatin. In contrast to the systematic administration of therapeutics via repeatedly intravenous injections of micelles, this implantable device has these capacities of greatly reducing the drug dose, the frequency of administration and side effect of chemotherapeutic agents while maintaining highly therapeutic efficacy against artificial solid tumors. This micelle-based nanofiber device can be developed toward the next generation of nanomedicine for efficient and safe cancer therapy.Keywords: active targeting; cancer therapy; localized drug delivery; nanocarrier; nanofibers;
Co-reporter:Xing Guo, Chunli Shi, Guang Yang, Jie Wang, Zhenghong Cai, and Shaobing Zhou
Chemistry of Materials 2014 Volume 26(Issue 15) pp:4405
Publication Date(Web):July 21, 2014
DOI:10.1021/cm5012718
Efficient delivery of therapeutic agents with nanocarriers into the nucleus to achieve high therapeutic efficiency is still a major challenge for cancer therapy due to mucosal barriers, nonspecific uptake, and intracellular drug resistance. In this study, we develop a dual-responsive polymer micelle system with sheddable polyethylenimine (PEI) shells for actively targeted drug delivery. This system exhibits an ultrasensitive negative-to-positive charge reversal in response to the extracellular pH value, resulting in greatly enhanced uptake by cancer cells via electrostatic interaction. Moreover, the active targeting ability can further promote the selective uptake of the nanocarriers in the cancer cell. Once the micelles escape from the lysosomes, the disulfide linkages can be cleaved by GSH in the cytoplasm, and in turn the hydrophilic PEI shell is deshielded, leading to the rapid release of the encapsulated agent into the nuclei. The antitumor activity in 4T1 tumor-bearing mice reveals that this novel system possesses a long blood circulation due to the originally negatively charged surface and can significantly promote the cell internalization and intracellular drug release, thus leading to a high therapeutic efficacy against resistant tumors and fewer side effects to normal tissues.
Co-reporter:Tao Gong, Kun Zhao, Wenxi Wang, Hongmei Chen, Lin Wang and Shaobing Zhou
Journal of Materials Chemistry A 2014 vol. 2(Issue 39) pp:6855-6866
Publication Date(Web):19 Aug 2014
DOI:10.1039/C4TB01155D
The particles that can reversibly switch shape in response to an environmental stimulus are preferable for controlling the performance of drug carriers. In this work, we present a facile strategy towards the design and fabrication of polymer particles that can reversibly switch their shape on the basis of a biocompatible and biodegradable polymer network containing well-defined six-arm poly(ethylene glycol)-poly(ε-caprolactone) (6A PEG-PCL). These polymer particles have a capacity of reversibly changing shape from spherical to elliptical either extracellularly or intracellularly with the cyclic heating and cooling between 43 °C and 0 °C under a stress-free condition via a reversible two-way shape memory effect (2W-SME) of a polymer matrix. This study of the shape-switching particles opens up exciting possibilities for engineering dynamically shape-switching drug delivery carriers to either avoid or promote phagocytosis.
Co-reporter:Xing Guo, Dan Li, Guang Yang, Chunli Shi, Zhaomin Tang, Jie Wang, and Shaobing Zhou
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 11) pp:8549
Publication Date(Web):April 30, 2014
DOI:10.1021/am501422r
How to deliver the drug to the target area at the right time and at the right concentration is still a challenge in cancer therapy. In this study, we present a facile strategy to control drug release by precisely controlling the thermo-sensitivity of the nanocarriers to the variation of environmental temperature. One type of thermoresponsive Pluronic F127-poly(d,l-lactic acid) (F127-PLA, abbreviated as FP) copolymer micelles was developed and decorated with folate (FA) for active targeting. FP100 micelles assembled from FP with PLA segment having polymerization degree of 100 had a low critical solution temperature of 39.2 °C close to body temperature. At 37 °C, little amount of encapsulated anticancer drug DOX is released from the FP100 micelles, while at a slightly elevated temperature (40 °C), the shrinkage of thermoresponsive segments causes a rapid release of DOX and instantly increases the drug concentration locally. The cytocompatibility analysis and cellular uptake efficiency were characterized with the fibroblast cell line NIH 3T3 and human cervix adenocarcinoma cell line HeLa. The results demonstrate that this copolymer has excellent cytocompatibility, and FA-decorated FP100 micelles present much better efficiency of cellular uptake and higher cytotoxicity to folate receptor (FR)-overexpressed HeLa cells. In particular, under hyperthermia (40 °C) the cytotoxicity of DOX-loaded FA-FP100 micelles against HeLa cells was significantly more obvious than that upon normothermia (37 °C). Therefore, these temperature-responsive micelles have great potential as a drug vehicle for cancer therapy.Keywords: active targeting; anticancer; drug delivery; nanotechnology; polymeric micelle; thermoresponsive;
Co-reporter:Xifeng Yang, Lin Wang, Wenxi Wang, Hongmei Chen, Guang Yang, and Shaobing Zhou
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 9) pp:6545
Publication Date(Web):March 11, 2014
DOI:10.1021/am5001344
In this study, we synthesized one type of star-shaped polyurethane (SPU) with star-shaped poly(ε-caprolactone) (SPCL) containing different arm numbers as soft segment and 4,4′-diphenyl methane diisocyanate (MDI) as well as chain extender 1,4-butylene glycol (BDO) as hard segment. Proton nuclear magnetic resonance (1H-NMR) confirmed the chemical structure of the material. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) results indicated that both the melting temperature (Tm) and transition temperature (Ttrans) of SPU decreased with the hard segment composition increase. X-ray diffraction (XRD) results demonstrated that the increase of the crystallinity of SPU following the raised arm numbers endowed a high shape fixity of six-arm star-shaped polyurethane (6S-PU) and a wide melting temperature range, which resulted in an excellent triple-shape memory effect of 6S-PU. The in vitro cytotoxicity assay evaluated with osteoblasts through Alamar blue assay demonstrates that this copolymer possessed good cytocompatibility. This material can be potentially used as a new smart material in the field of biomaterials.Keywords: biocompatibility; crystallinity; star-shaped polyurethane; triple-shape memory effect; wide melting range;
Co-reporter:Hongmei Chen, Ying Li, Ye Liu, Tao Gong, Lin Wang and Shaobing Zhou
Polymer Chemistry 2014 vol. 5(Issue 17) pp:5168-5174
Publication Date(Web):02 May 2014
DOI:10.1039/C4PY00474D
In this study, a highly pH-sensitive polymer is synthesised by introducing pyridine rings into the backbone of polyurethane. The chemical structures of the resulting materials are confirmed by FT-IR and 1H-NMR spectroscopy. To analyse the mechanism of the pH sensitivity of this polymer, its structural transformations under acidic and basic conditions are studied by FT-IR spectroscopy, theoretical calculations and 1H-NMR spectroscopy. We observe that the mechanism of pH responsiveness is the formation of a hydrogen bond interaction between the N atom of the pyridine ring and H–N of urethane in neutral or alkaline environments which is disrupted under acidic conditions due to the protonation of the pyridine ring. The pH-sensitivity is demonstrated by simply adjusting the pH value of the environment, which can act as a switch to control shape memory and drug release. Unlike other systems with thermally sensitive behaviour, the shape memory functionality of this material is independent of temperature, which is dependent only on the variation in the pH of the environment. This strategy provides a potent tool for the design of multifunctional materials based on the physiological environment to fulfil the complex requirements of drug delivery and tissue engineering systems.
Co-reporter:Xian Liu, Kun Zhao, Tao Gong, Jian Song, Chongyun Bao, En Luo, Jie Weng, and Shaobing Zhou
Biomacromolecules 2014 Volume 15(Issue 3) pp:
Publication Date(Web):January 28, 2014
DOI:10.1021/bm401911p
Implantation of a porous scaffold with a large volume into the body in a convenient and safe manner is still a challenging task in the repair of bone defects. In this study, we present a porous smart nanocomposite scaffold with a combination of shape memory function and controlled delivery of growth factors. The shape memory function enables the scaffold with a large volume to be deformed into its temporal architecture with a small volume using hot-compression and can subsequently recover its original shape upon exposure to body temperature after it is implanted in the body. The scaffold consists of chemically cross-linked poly(ε-caprolactone) (c-PCL) and hydroxyapatite nanoparticles. The highly interconnected pores of the scaffold were obtained using the sugar leaching method. The shape memory porous scaffold loaded with bone morphogenetic protein-2 (BMP-2) was also fabricated by coating the calcium alginate layer and BMP-2 on the surface of the pore wall. Under both in vitro and in vivo environmental conditions, the porous scaffold displays good shape memory recovery from the compressed shape with deformed pores of 33 μm in diameter to recover its porous shape with original pores of 160 μm in diameter. In vitro cytotoxicity based on the MTT test revealed that the scaffold exhibited good cytocompatibility. The in vivo micro-CT and histomorphometry results demonstrated that the porous scaffold could promote new bone generation in the rabbit mandibular bone defect. Thus, our results indicated that this shape memory porous scaffold demonstrated great potential for application in bone regenerative medicine.
Co-reporter:Lin Wang, Xifeng Yang, Hongmei Chen, Tao Gong, Wenbing Li, Guang Yang, and Shaobing Zhou
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 21) pp:10520
Publication Date(Web):September 30, 2013
DOI:10.1021/am402091m
A triple-shape memory polyurethane (TSMPU) with poly(ε-caprolactone) -diols (PCL-diols) as the soft segments and diphenyl methane diisocyanate (MDI), N,N-bis (2-hydroxyethyl) cinnamamide (BHECA) as the hard segments was synthesized via simple photo-crosslinking of cinnamon groups irradiated under λ > 280 nm ultraviolet (UV) light. Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) and ultraviolet-visible absorption spectrum (UV–vis) confirmed the chemical structure of the material. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) results demonstrated that the photo-crosslinked polymer possessed two transition temperatures, one is due to the melting point of the soft segment PCL-diols, and the other is due to the glass transition temperature. All these contributed to the cross-linked structure of the hard segments and resulted in an excellent triple-shape memory effect. Alamar blue assay showed that the material has good non-cytotoxicity and can be potentially used in biomaterial devices.Keywords: cinnamate group; photo crosslink; polyurethane; triple shape memory;
Co-reporter:Lin Wang, Xifeng Yang, Hongmei Chen, Guang Yang, Tao Gong, Wenbing Li and Shaobing Zhou
Polymer Chemistry 2013 vol. 4(Issue 16) pp:4461-4468
Publication Date(Web):24 May 2013
DOI:10.1039/C3PY00519D
A multi-stimuli sensitive shape memory poly(vinyl alcohol)-graft-polyurethane was synthesized. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR) confirmed the chemical structure of the material. The material exhibits good water-induced shape memory behavior and a thermally induced dual shape memory effect. Further study indicated that the material exhibits good triple shape memory behavior. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) demonstrated that the polymer possesses a wide transition temperature, which resulted in excellent dual- and triple-shape memory effects. DSC and swelling experiments were carried out to find that the mechanism of the water-induced shape memory effect involves the decrease of the transition temperature when it swelled in water. Alamar Blue assay showed that the material possesses good biocompatibility and can be potentially used in the field of biomaterials.
Co-reporter:Shan Ding, Jinrong Li, Chao Luo, Long Li, Guang Yang and Shaobing Zhou
Biomaterials Science 2013 vol. 1(Issue 10) pp:1091-1100
Publication Date(Web):17 Jul 2013
DOI:10.1039/C3BM60095E
Stem cells can alter their shapes and functions in response to the physical cues at the cell–substrate interface or the chemical signals in the culture environment. In this study, the surface nanoroughness, as a physical cue in the form of the beads-on-string features on polymer nanofibers, was fabricated through an electrospinning technology, and simultaneously dexamethasone (DEX), an osteogenic differentiation factor as a chemical signal, was incorporated into these nanofibers during this process. The morphology of the DEX-loaded nanofibers was observed with scanning electron microscopy (SEM). In vitro DEX release was carried out in PBS over a period of 29 days. The combination of the physical and chemical signals was also used to investigate the differentiation capability of rat bone marrow mesenchymal stem cells (rBMSCs) through SEM and fluorescence microscopy observation, alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, quantification of mineral deposition and quantitative real-time PCR analysis. The results indicate that the DEX gradually released into the culture medium played a dominant role in promoting rBMSCs’ differentiation towards osteoblast-like cells, and the surface nanoroughness could play a supporting role in the differentiation. Therefore, this DEX-loaded polymer nanofiber scaffold with moderate surface nanoroughness has great potential application in bone tissue regeneration.
Co-reporter:Tao Chen, Xing Guo, Aijun Zhao, Jie Wang, Chunli Shi and Shaobing Zhou
Soft Matter 2013 vol. 9(Issue 11) pp:3021-3031
Publication Date(Web):22 Jan 2013
DOI:10.1039/C2SM27173G
Biodegradable micelles were fabricated by self-assembly in the aqueous solution of PEG-based ether-anhydride terpolymer consisting of poly(ethylene glycol) (PEG), 1,3-bis(p-carboxyphenoxy) propane (CPP) and sebacic acid (SA). Morphological transition of the micelles was investigated in terms of PEG chain length, hydrophilic–hydrophobic segment ratio, polymer concentration and environmental temperature. The effect of micellar shape on drug loading capacity and cytotoxicity was evaluated. The cellular uptake efficiency was characterized qualitatively with the human hepatoblastoma cell lines (HepG2) and fibroblast normal cells by fluorescence microscopy. Primary in vivo biodistribution of the drug-loaded micelles with diverse morphologies in tumor and normal tissues was also assessed using 4T1 bearing mice. The results show that terpolymer micelles with rod-like shape possess better biocompatibility and the in vivo biodistribution is dependent on micellar shape. Therefore, these polymer micelles have great potential as a novel drug vehicle in nanomedicine.
Co-reporter:Hongmei Chen, Ye Liu, Tao Gong, Lin Wang, Keqing Zhao and Shaobing Zhou
RSC Advances 2013 vol. 3(Issue 19) pp:7048-7056
Publication Date(Web):01 Mar 2013
DOI:10.1039/C3RA00091E
We have developed a simple and controllable strategy to synthesize a triple-shape memory supermolecular composite (SMPU-INCh-n) through H-bonding interactions between a polymer and mesogenic units. The polymer is shape memory polyurethane (SMPU) with carboxyl groups; the mesogenic unit, named as cholesteryl isonicotinate (INCh), is a liquid crystal compound with an electron-rich pyridine ring. The H-bonding interactions between carboxyl and pyridine ring are proved by FT-IR spectroscopic analysis and 1H solid-state NMR. The introducing of INChs promotes the bonded PU segments to change into glassy form by restraining the movement of polymer chains, which is responsible for the triple-shape memory property. Therefore, the composite presents excellent triple-shape effect, and may be of great potential for applications in the biomedical field.
Co-reporter:Tao Gong, Wenbing Li, Hongmei Chen, Lin Wang, Shijun Shao, Shaobing Zhou
Acta Biomaterialia 2012 Volume 8(Issue 3) pp:1248-1259
Publication Date(Web):March 2012
DOI:10.1016/j.actbio.2011.12.006
Abstract
One class of biodegradable polymer composite nanofibers was fabricated with an electrospinning process using chemically cross-linked poly(ε-caprolactone) (c-PCL) as the matrix and multiwalled carbon nanotubes (MWNTs) as the reinforced filler coated with Fe3O4 nanoparticles as a magnetism responsive source. The composite fibers showed an excellent shape memory effect, triggered both by hot water and by an alternating magnetic field. The heat in the PCL matrix generated from magnetic nanoparticles via hysteresis loss in the magnetic field was also determined quantitatively. The Fe3O4-loaded MWNT composite nanoparticles (Fe3O4@CD-M) were synthesized through two steps: (1) the raw MWNTs were firstly functionalized by grafting maleic anhydride (MA) on their surface through a free radical reaction and later covalently modified by β-cyclodextrin (β-CD) through an esterification reaction; (2) Fe3O4@CD-M composite nanoparticles were prepared by chemical co-precipitation of Fe2+ and Fe3+ ions on the surface of the β-CD functionalized MWNTs with an electrostatic self-assembly approach using β-CD as the depositional locus. Alamar blue assay was also performed from culturing osteoblast populations to evaluate the cytotoxicity. The result showed that the electrospun composite fibers possessed good biocompatibility and could be applied in biomedical fields.
Co-reporter:Qi Zhou, Zhao Zhang, Tao Chen, Xing Guo, Shaobing Zhou
Colloids and Surfaces B: Biointerfaces 2011 Volume 86(Issue 1) pp:45-57
Publication Date(Web):1 August 2011
DOI:10.1016/j.colsurfb.2011.03.013
The mixed micelles composed of pluronic F127-b-poly(ɛ-caprolactone) (F127-CL) and bovine serum albumin (BSA) or polylactic acid (PLA) were fabricated for application as promising drug carriers. F127-CL copolymers were characterized by 1H NMR, FT-IR, GPC, DSC, XRD and POM. They can self-assemble into micelles in water by solvent evaporation method. The thermo-responsivities of the pure and mixed micelles were investigated. The drug release behaviors were investigated in phosphate-buffered solution (PBS) and acetate buffer solution (ABS), respectively, at 37 °C. The hemolysis and coagulation assay and the tumor cell growth inhibition assays were further evaluated. The morphologies of pure micelles underwent from the coexistence of the rods and spheres to the spheres with increasing the lengths of CL. The micelle behaviors were influenced with the addition of BSA and PLA. Both pure and mixed micelles of F127-CL with CL length of 200 show thermo-responsivities from 25 to 45 °C, while form larger aggregations at high temperature. The hemolysis and coagulation assays showed that the micelles possess good blood compatibility. The cytotoxicity results showed that the copolymer was a safe carrier and the encapsulated doxorubicind.HCl remained its potent anti-tumor effect. The in vitro release profiles displayed a sustained release of DOX.HCl from the micelles. The block copolymers can be great potential as a nanocontainer in drug delivery systems.Graphical abstractHighlights► The mixed micelles composed of F127-CL copolymer and BSA or PLA display good thermosensitivity. ► The release of DOX.HCl from the micelles is faster in mildly acidic physiological environments than that at pH 7.4. ► The micelles possess excellent biocompatibility. ► The DOX.HCl-loaded micelles are effective to inhibit the growth of HepG2 tumor cells.
Co-reporter:Qi Zhou, Xing Guo, Tao Chen, Zhao Zhang, Shijun Shao, Chao Luo, Jinrong Li, and Shaobing Zhou
The Journal of Physical Chemistry B 2011 Volume 115(Issue 43) pp:12662-12670
Publication Date(Web):September 26, 2011
DOI:10.1021/jp207951e
For cancer therapy, folate (FA) and β-cyclodextrin (β-CD) decorated micelles based on the biodegradable pluronic F127-b-poly(ε-caprolactone) copolymer were fabricated. These micelles were measured by dynamic light scattering measurements and atomic force microscopy. The in vitro release of doxorubicin hydrochloride (DOX·HCl) from the biodegradable polymer micelles was performed in a phosphate-buffered saline solution at pH 7.4 and acetate buffer solution at pH 5.0 at the temperatures of 4, 25, and 37 °C, and the results show that the release was obviously influenced by the pH and temperature. The material cytotoxicity and the tumor cell growth inhibition assays of DOX·HCl-loaded micelles were studied with the human hepatoblastoma cell line (HepG2), the lung epithelial cancer cell line (A549), and human nasopharyngeal epidermoid carcinoma cells (KB) and fibroblast normal cells using fluorescence microscopy as well as confocal laser scanning microscopy. The cellular uptake was quantitatively analyzed to further evaluate the active targeting behaviors of the micelles by flow cytometry. These quantitative and qualitative results of cellular uptake of the micelles provide evidence for the different targeting efficiencies of FA decoration for HepG2, KB, and A549 tumor cells as well as fibroblast normal cells. It also suggested that FA- and β-CD-decorated doxorubicin-loaded micelles may have great potential as nanocarriers for targeted drug delivery.
Co-reporter:Yu Xiao, Shaobing Zhou, Lin Wang, and Tao Gong
ACS Applied Materials & Interfaces 2010 Volume 2(Issue 12) pp:3506
Publication Date(Web):November 19, 2010
DOI:10.1021/am100692n
One type of electroactive shape memory nanocomposite was fabricated, including cross-linked poly(ε-caprolactone) (cPCL) and conductive multiwalled carbon nanotubes (MWNTs). The cross-linking reaction of the pristine poly(ε-caprolactone) (PCL) was realized by using benzoyl peroxide (BPO) as an initiator. The raw MWNTs (Raw-M) were prefunctionalized by acid-oxidation process and covalent grafting with poly (ethylene glycol) (PEG), respectively. Three kinds of nanocomposites containing cPCL/Raw-M, cPCL/acid-oxidation MWNTs (AO-M) and cPCL/PEG grafted MWNTs (PEG-M) were obtained, and the mechanical, electrical and shape memory properties were further investigated. The influence of in vitro degradation on their shape memory and mechanical properties was also evaluated. The methyl thiazolyl tetrazolium (MTT) assay was performed to estimate their biocompatibility. The results displayed that these nanocomposites could perform favorable shape memory recovery both in hot water at 55 °C and in electric field with 50 V applied voltage. In addition, compared with cPCL/Raw-M and cPCL/AO-M, cPCL/PEG-M composite possessed more favorable properties such as mechanical, biocompatible, and electroactive shape memory functions. Therefore, the nanocomposite may be potential for application as smart bioactuators in biomedical field.Keywords: biodegradable; carbon nanotube; nanocomposites; shape memory
Co-reporter:Aijun Zhao;Qi Zhou;Tao Chen;Jie Weng
Journal of Applied Polymer Science 2010 Volume 118( Issue 6) pp:3576-3585
Publication Date(Web):
DOI:10.1002/app.32724
Abstract
A series of amphiphilic poly(ether-anhydrides) terpolymers composed of sebacic acid, 1,3-bis(carboxyphenoxy) propane, and poly(ethylene glycol) (PEG) were synthesized via melt-condensation polymerization. The resultant terpolymers were characterized by 1H-nuclear magnetic resonance spectroscopy (1H-NMR), Fourier transform infrared spectroscopy, gel permeation chromatography, X-ray diffraction, polarization optical microscope, differential scanning calorimeter, and water contact angle. Biodegradable micelles were prepared via a precipitation method through self-emulsification. The shape of these micelles was uniform and spheric according to the atomic force microscopy and transmission electron microscopy images. The dynamic light scattering measurements indicated that the diameters of micelles were typically in the range of 118–359 nm. The results displayed the PEG-based ether-anhydride terpolymers may be of great potential as nanoscaled carriers for drug delivery system. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Co-reporter:Aijun Zhao;Qi Zhou;Tao Chen
Pharmaceutical Research 2010 Volume 27( Issue 8) pp:1627-1643
Publication Date(Web):2010 August
DOI:10.1007/s11095-010-0155-1
The thermosensitive micelles based on the poly(PEG:CPP:SA) terpolymer composed of poly(ethylene glycol) (PEG), 1,3-bis(carboxyphenoxy) propane (CPP) and sebacic acid (SA) were fabricated for application as a promising drug carrier.The terpolymer can self-assemble into micelles in water by a precipitation technology. The sol–gel transition behaviors were investigated by the tube-tilting method and dynamic rheology. The drug release behaviors were investigated in phosphate-buffered solution (PBS) at 25, 37 and 45°C, respectively, and the tumor cell growth inhibition assays were also evaluated.The diameters of these micelles increased as the environmental temperature, and the length of CPP and SA chains increased. The micelles with a low concentration underwent sol-to-nanogel transition as temperature increased from the room temperature to the body temperature, while the polymer solutions with a high concentration underwent sol-to-gel transition as the temperature increased from 20 to 70°C. In vitro release profiles consisted of a burst release followed a sustained release. The cytotoxicity results showed that the terpolymer micelles were biocompatible, and the encapsulated doxorubicin. HCl maintained its potent anti-tumor effect.These micelles may bring the ether-anhydride family of polymers great potential as a novel carrier in nanomedicine.
Co-reporter:Yu Xiao, Tao Gong, Shaobing Zhou
Biomaterials 2010 31(19) pp: 5182-5190
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.03.012
Co-reporter:Lin Sun;Weijia Wang
Journal of Materials Science: Materials in Medicine 2009 Volume 20( Issue 10) pp:2035-2042
Publication Date(Web):2009 October
DOI:10.1007/s10856-009-3765-6
Poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride) (P(CPP-SA)) have the anhydride bonds in copolymer backbone, which are available for degradation on the base of passive hydrolysis. This chemical structure made it degraded within a short time in linear degradation rate. For this property, polyanhydrides are one of the most suitable biodegradable polymers employed as drug carriers. This paper aimed at researching the erosion and degradation of P(CPP-SA) microspheres with CPP/SA monomer ratios of 20:80, 35:65 and 50:50. In vitro protein release from the microspheres was also investigated in this paper. Human serum albumin (HSA) was used as the model protein. In this research, the microspheres degradation and drug release rate from microspheres can be adjusted by altering the CPP/SA ratios of P(CPP-SA). The features of surface erosion were observed in SEM. The structural integrity of HSA extracted from microspheres was detected by gel permeation chromatography, compared with native HSA. The results showed HSA remained its molecule weight after encapsulated.
Co-reporter:Xiaotong Zheng, Shaobing Zhou, Yu Xiao, Xiongjun Yu, Xiaohong Li, Peizhuo Wu
Colloids and Surfaces B: Biointerfaces 2009 Volume 71(Issue 1) pp:67-72
Publication Date(Web):1 June 2009
DOI:10.1016/j.colsurfb.2009.01.009
In this paper, the preparation of biocompatible poly(d,l-lactide) (PDLLA)/magnetite (Fe3O4) nanocomposites and their shape memory effect are reported. Fe3O4 nanoparticles with an average size of 20 nm were synthesized by chemical co-precipitation and mixed uniformly with a PDLLA matrix. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and mechanical testing were carried out to determine the micro-surface morphology, glass transition temperature (Tg), functional groups change and mechanical properties of the PDLLA/Fe3O4 nanocomposites. The interesting shape memory behavior of the nanocomposites induced by an ultrasonic alternating magnetic field were also observed. SEM and DSC showed that there was a close interaction between the polymer matrix and the magnetic nanoparticles. Formation of weak hydrogen bonds between the CO in PDLLA and Fe–OH groups of the surface of nano-crystalline Fe3O4 was examined by FTIR. The PDLLA/Fe3O4 nanocomposites displayed a desirable shape memory effect.
Co-reporter:Xiaotong Zheng;Yu Xiao;Xiongjun Yu ;Bo Feng
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2009 Volume 91B( Issue 1) pp:
Publication Date(Web):
DOI:10.1002/jbm.b.31388
Abstract
A novel biodegradable polymer–ceramic nanocomposite was prepared using the in situ preparation method, which consisted of gelatin (gel), poly(D,L-lactide) (PDLLA), and hydroxyapatite (HA) nanofibers. In this article, the HA nanofibers with length/diameter (L/D) ratio of 19.8 in gel/PDLLA/HA nanocomposites were synthesized and precipitated in polymeric matrix by one-step hydrothermal mineralization. The crystalline phases, structural morphology, mechanical characterization, and chemical interaction of gel/PDLLA/HA nanocomposites were investigated by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, mechanical test, and Fourier transform infrared spectroscopy. The results showed that the crystalline HA nanofibers were uniformly mineralized in gel and PDLLA matrix and the interaction between Ca2+ in HA (nanofibers and negative-charged functional groups in gel and PDLLA molecular chains was formed. Thus, the schematic model of two polymeric chains bridged by inorganic nanofibers was designed on the basis of the experimental results. Moreover, it can clearly explain why the mechanical properties of gel/PDLLA/HA nanocomposites turned strong. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Co-reporter:Shaobing Zhou;Jing Sun;Lin Sun;Yanqin Dai;Liping Liu;Xiaohong Li;Jianxin Wang;Jie Weng;Wenxiang Jia;Zairong Zhang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2008 Volume 87B( Issue 1) pp:189-196
Publication Date(Web):
DOI:10.1002/jbm.b.31091
Abstract
In this work, magnetite (Fe3O4) nanoparticles with an average size 10 nm modified by sodium oleate were prepared by the modified controlled chemical coprecipitation method, which can be well dispersed in water and linked well with protein molecules because of the presence of —COOH on their surface. Then magnetic poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres containing interferon alpha-2b (IFN-a-2b) were prepared by the modified water-in-oil-in-water solvent evaporation procedure. X-ray powder diffraction analysis, particle size analysis, transmission electron microscopy, scanning electron microscopy, and vibrating-sample magnetometer (VSM) analysis were carried out to examine phase composition, surface and interior morphology, size and size distribution, and magnetic properties of the magnetic microspheres. Also the effects of some important parameters on the magnetic biodegradable microspheres were investigated, such as magnetite dosage in the preparation system, stirring rate of the suspension medium, and concentration of the external aqueous phase. And the antiviral activity of IFN-a-2b encapsulated in the magnetic polymeric microspheres was evaluated by the vesicular stomatitis virus (VSV) cytopathicity inhibition assay. The results showed that the properties of IFN-loaded magnetic PLGA and PLA microspheres were better than the conventional protein-loaded polymeric microspheres, such as perfect magnetic properties, higher protein encapsulation efficiency, and less effect on the antiviral activity of protein. These indicated that the magnetic PLA and PLGA microspheres containing IFN-a-2b exhibited strong potential as targeted-drug delivery vehicles, which could be rapidly localized to the immunization-related tissues easily by an external magnetic field. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008
Co-reporter:Shaobing Zhou, Hongsen Peng, Xiongjun Yu, Xiaotong Zheng, Wenguo Cui, Zairong Zhang, Xiaohong Li, Jianxin Wang, Jie Weng, Wenxiang Jia and Fei Li
The Journal of Physical Chemistry B 2008 Volume 112(Issue 36) pp:11209-11216
Publication Date(Web):August 19, 2008
DOI:10.1021/jp800913k
In the paper, we successfully prepared spider silk fibroins (Ss)/poly(d,l-lactide) (PDLLA) composite fibrous nonwoven mats for the first time to the best of our knowledge. The morphology of the fibers was observed by a scanning electron microscope (SEM) and transmission electron microscope (TEM). The secondary structure change of the spidroin before and after electrospinning was characterized using Fourier transform infrared spectroscopy (FT-IR). Herein, a qualitative analysis of the conformational changes of the silk protein was performed by analyzing the FT-IR second-derivative spectra, from which quantitative information was obtained via the deconvolution of the amide I band. A mechanical test was carried out to investigate the tensile strength and the elongation at break. A water contact angle (CA) measurement was also performed to characterize surface properties of the fibers. The cytotoxicity of electrospun PDLLA and Ss−PDLLA nonwoven fibrous mats was evaluated based on a CCL 81(Vero) cells proliferation study. The results showed that the hydrophilic and mechanical property of the composite fiber were improved by introducing spidroin.
Co-reporter:Tao Gong, Kun Zhao, Wenxi Wang, Hongmei Chen, Lin Wang and Shaobing Zhou
Journal of Materials Chemistry A 2014 - vol. 2(Issue 39) pp:NaN6866-6866
Publication Date(Web):2014/08/19
DOI:10.1039/C4TB01155D
The particles that can reversibly switch shape in response to an environmental stimulus are preferable for controlling the performance of drug carriers. In this work, we present a facile strategy towards the design and fabrication of polymer particles that can reversibly switch their shape on the basis of a biocompatible and biodegradable polymer network containing well-defined six-arm poly(ethylene glycol)-poly(ε-caprolactone) (6A PEG-PCL). These polymer particles have a capacity of reversibly changing shape from spherical to elliptical either extracellularly or intracellularly with the cyclic heating and cooling between 43 °C and 0 °C under a stress-free condition via a reversible two-way shape memory effect (2W-SME) of a polymer matrix. This study of the shape-switching particles opens up exciting possibilities for engineering dynamically shape-switching drug delivery carriers to either avoid or promote phagocytosis.
Co-reporter:Shan Ding, Jinrong Li, Chao Luo, Long Li, Guang Yang and Shaobing Zhou
Biomaterials Science (2013-Present) 2013 - vol. 1(Issue 10) pp:NaN1100-1100
Publication Date(Web):2013/07/17
DOI:10.1039/C3BM60095E
Stem cells can alter their shapes and functions in response to the physical cues at the cell–substrate interface or the chemical signals in the culture environment. In this study, the surface nanoroughness, as a physical cue in the form of the beads-on-string features on polymer nanofibers, was fabricated through an electrospinning technology, and simultaneously dexamethasone (DEX), an osteogenic differentiation factor as a chemical signal, was incorporated into these nanofibers during this process. The morphology of the DEX-loaded nanofibers was observed with scanning electron microscopy (SEM). In vitro DEX release was carried out in PBS over a period of 29 days. The combination of the physical and chemical signals was also used to investigate the differentiation capability of rat bone marrow mesenchymal stem cells (rBMSCs) through SEM and fluorescence microscopy observation, alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, quantification of mineral deposition and quantitative real-time PCR analysis. The results indicate that the DEX gradually released into the culture medium played a dominant role in promoting rBMSCs’ differentiation towards osteoblast-like cells, and the surface nanoroughness could play a supporting role in the differentiation. Therefore, this DEX-loaded polymer nanofiber scaffold with moderate surface nanoroughness has great potential application in bone tissue regeneration.
![Poly[oxy(1-methyl-2-oxo-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ester with α-methyl-ω-hydroxypoly(oxy-1,2-ethanediyl), diblock](http://img.cochemist.com/ccimg/188400/188360-48-7.png)
![Poly[oxy(1-methyl-2-oxo-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ester with α-methyl-ω-hydroxypoly(oxy-1,2-ethanediyl), diblock](http://img.cochemist.com/ccimg/188400/188360-48-7_b.png)
![N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid 5-(2,5-dioxo-1-pyrrolidinyl) ester](http://img.cochemist.com/ccimg/153500/153445-05-7.png)
![N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid 5-(2,5-dioxo-1-pyrrolidinyl) ester](http://img.cochemist.com/ccimg/153500/153445-05-7_b.png)
![Benzoic acid,4,4'-[1,3-propanediylbis(oxy)]bis-, homopolymer](http://img.cochemist.com/ccimg/90500/90409-77-1.png)
![Benzoic acid,4,4'-[1,3-propanediylbis(oxy)]bis-, homopolymer](http://img.cochemist.com/ccimg/90500/90409-77-1_b.png)
![Poly[oxy(1,10-dioxo-1,10-decanediyl)]](http://img.cochemist.com/ccimg/27000/26913-47-3.png)
![Poly[oxy(1,10-dioxo-1,10-decanediyl)]](http://img.cochemist.com/ccimg/27000/26913-47-3_b.png)
![Benzenesulfonic acid,4-[2-[4-(dimethylamino)phenyl]diazenyl]-](http://img.cochemist.com/ccimg/600/502-02-3.png)
![Benzenesulfonic acid,4-[2-[4-(dimethylamino)phenyl]diazenyl]-](http://img.cochemist.com/ccimg/600/502-02-3_b.png)
![Carbamic acid, N-[2-[(2-aminoethyl)dithio]ethyl]-, 1,1-dimethylethyl ester](/data/chemimg/105100/485800-26-8.png)
![Carbamic acid, N-[2-[(2-aminoethyl)dithio]ethyl]-, 1,1-dimethylethyl ester](/data/chemimg/105100/485800-26-8_b.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4_b.png)
