XiuLi Zhuang

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Name: 庄秀丽; XiuLi Zhuang

Organization: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , China

Department: State Key Laboratory of Polymer Physics and Chemistry

Title: Researcher/Professor(PhD)

TOPICS

Material Chemistry

Polymer

Chemicals
References

Efficacious hepatoma-targeted nanomedicine self-assembled from galactopeptide and doxorubicin driven by two-stage physical interactions

Co-reporter:Jianxun Ding, Chunsheng Xiao, Yuce Li, Yilong Cheng, Nannan Wang, Chaoliang He, Xiuli Zhuang, Xiaojuan Zhu, Xuesi Chen

Journal of Controlled Release 2013 Volume 169(Issue 3) pp:193-203

Publication Date(Web):10 August 2013

DOI:10.1016/j.jconrel.2012.12.006

Polymers bearing pendant galactosyl group are attractive for targeted intracellular antitumor drug delivery to hepatoma cells (e.g. HepG2 and SMMC7721 cells) with asialoglycoprotein receptor (ASGP-R). Herein, a series of galactopeptides was synthesized through ring-opening polymerization of L-glutamate N-carboxyanhydride, deprotection of benzyl group and subsequent Huisgens cycloaddition “click” reaction with azide-modified galactosyl group. The copolypeptides were revealed to have excellent hemocompatibilities, and cell and tissue compatibilities, which rendered their potential for drug delivery applications. The hepatoma-targeted micellar nanoparticle (i.e. nanomedicine) was fabricated by cooperative self-assembly of galactopeptide and doxorubicin (DOX) induced by two-stage physical interactions. In vitro DOX release from nanomedicine was accelerated in the intracellular acidic condition. Through the recognition between galactose ligand and ASGP-R of HepG2 cells, the endocytosis of galactosylated nanomedicine was significantly promoted, which was demonstrated by confocal laser scanning microscopy and flow cytometry. Remarkably, the galactose-decorated nanomedicine retained much higher antitumor activity toward HepG2 cells in contrast to the nanomedicine without galactosyl group in vitro and in vivo. The above superiorities indicated that the galactosylated nanomedicine possessed great promising for hepatoma-targeted chemotherapy.

Thermo-responsive “hairy-rod” polypeptides for smart antitumor drug delivery

Co-reporter:Jianxun Ding, Li Zhao, Di Li, Chunsheng Xiao, Xiuli Zhuang and Xuesi Chen

Polymer Chemistry 2013 vol. 4(Issue 11) pp:3345-3356

Publication Date(Web):14 Mar 2013

DOI:10.1039/C3PY00144J

A series of thermo-responsive “hairy-rod” polypeptides was efficiently synthesized by grafting of azide-terminated (co)polymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) or 2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate (MEO3MA) (i.e., N3-PMEOiMA) onto poly(γ-propargyl-L-glutamate) (PPLG) through a “click” reaction. The thermo-responsiveness and secondary structure of the resultant polypeptides (i.e. PLG-g-PMEOiMA) were shown to be dependent on the MEO2MA:MEO3MA ratio in PMEOiMA side chains. PLG40-g-P(MEO2MA18-co-MEO3MA9) (P2) and PLG40-g-P(MEO2MA7-co-MEO3MA18) (P4) with lower critical solution temperatures at 25.6 and 34.8 °C, and cloud points at 26.9 and 35.6 °C in physiological saline, respectively, were selected to self-assemble into micelles for doxorubicin (DOX) loading and release. In vitro DOX release from DOX-loaded micelles could be accelerated by a decrease of temperature and pH. Confocal laser scanning microscopy and flow cytometry confirmed the efficient internalization and intracellular DOX release of DOX-loaded micelles towards HeLa cells (a human cervical carcinoma cell line). In vitro methyl thiazolyl tetrazolium assays revealed that the polypeptides were cytocompatible, and DOX-loaded micelles showed efficient cellular proliferation inhibition. Hemolysis tests indicated that micelles were hemocompatible, and the encapsulation with polypeptides significantly reduced the hemolysis ratio of DOX. Therefore, the thermo-responsive polypeptide micelles, which are stable in physiological condition while releasing payloads in the acidic intracellular microenvironment, are promising for smart drug delivery.

Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy

Co-reporter:Jianxun Ding, Fenghua Shi, Di Li, Li Chen, Xiuli Zhuang and Xuesi Chen

Biomaterials Science 2013 vol. 1(Issue 6) pp:633-646

Publication Date(Web):08 Apr 2013

DOI:10.1039/C3BM60024F

Three derivatives of doxorubicin (DOX) were prepared by modifying DOX with succinic anhydride, cis-aconitic anhydride and 2,3-dimethylmaleic anhydride, generating acid-insensitive succinyl-DOX (SAD), acid-sensitive cis-aconityl-DOX (CAD) and 2,3-dimethylmaleyl-DOX (DAD) respectively. The pH and reduction dual-responsive methoxy poly(ethylene glycol)-poly(L-lysine-co-L-cystine) nanogel was employed to encapsulate the DOX derivatives. In vitro release studies showed that drug release could be accelerated in the intracellular acidic and reductive conditions. Confocal laser scanning microscopy and flow cytometry results demonstrated that an enhanced intracellular drug release was observed in glutathione monoester pretreated HeLa cells (a human cervical cell line). The DOX derivatives exhibited a lower accumulation in the nuclei than DOX. Moreover, the CAD and DAD-loaded nanogels showed a comparable anti-proliferative activity to the DOX-loaded nanogel against HeLa and HepG2 cells (a human hepatoma cell line). As a comparison, the SAD-loaded nanogel almost never inhibited cellular proliferation. The above results suggested that the pH and reduction dual-responsive nanogel can efficiently deliver acid-sensitive DOX derivatives into the nuclei of cancer cells for minimizing the side effects and enhancing the inhibition of cellular proliferation.

Redox-Sensitive Shell-Crosslinked Polypeptide-block-Polysaccharide Micelles for Efficient Intracellular Anticancer Drug Delivery

Co-reporter:Aiping Zhang;Zhe Zhang;Fenghua Shi;Chunsheng Xiao;Jianxun Ding;Chaoliang He;Li Chen;Xuesi Chen

Macromolecular Bioscience 2013 Volume 13( Issue 9) pp:1249-1258

Publication Date(Web):

DOI:10.1002/mabi.201300175

Redox-responsive SCMs based on amphiphilic PBLG-b-dextran with good biocompatibility are synthesized and used for efficient intracellular drug delivery. The molecular structures and SCMs characteristics are characterized by ¹H NMR, FT-IR, TEM, and DLS. The hydrodynamic radius of SCMs increases gradually in PBS due to the cleavage of disulfide bond in micellar shell caused by the presence of GSH. The encapsulation efficiency and release kinetics of DOX are investigated. The fastest DOX release is observed under intracellular-mimicking reductive environments. An MTT assay demonstrates that DOX-loaded SCMs show higher cellular proliferation inhibition against GSH-OEt pretreated HeLa and HepG2 than that of the non-pretreated and BSO-pretreated ones.

Synthesis of pH-responsive starch nanoparticles grafted poly (l-glutamic acid) for insulin controlled release

Co-reporter:Zhe Zhang, Hongling Shan, Li Chen, Chaoliang He, Xiuli Zhuang, Xuesi Chen

European Polymer Journal 2013 Volume 49(Issue 8) pp:2082-2091

Publication Date(Web):August 2013

DOI:10.1016/j.eurpolymj.2013.04.032

•In this article a novel oral protein drug delivery SNP-g-PGA was synthesized by click reaction.•The copolymer could assemble into amphiphilic aggregates with excellent pH-dependent property.•The loaded-insulin released from the copolymers more slowly at pH = 1.2 than that at pH = 6.8.In this article, a novel oral protein drug delivery made of starch nanoparticles (SNPs) as backbone and poly (l-glutamic acid) (PGA) as graft chains was successfully synthesized by click reaction. The grafting efficiency and structure of the resultant copolymer SNP-g-PGA were verified by 1H NMR and FT-IR spectra. The copolymer could assemble into amphiphilic aggregates. Hydrodynamic radii (Rh) of the aggregate decreased obviously as increasing pH value due to its excellent pH-dependent property. To take advantage of this pH-responsive property, in vitro insulin release experiment was carried out. The loaded-insulin released from the copolymers more slowly in artificial gastric juice (pH = 1.2) than that in artificial intestinal liquid (pH = 6.8) due to the excellent stability in acidic condition. These results suggested that the natural starch based material with pH sensitivity could be a promising delivery for insulin controlled release.Graphical abstract

Intracellular microenvironment responsive PEGylated polypeptide nanogels with ionizable cores for efficient doxorubicin loading and triggered release

Co-reporter:Fenghua Shi, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Chaoliang He, Li Chen and Xuesi Chen

Journal of Materials Chemistry A 2012 vol. 22(Issue 28) pp:14168-14179

Publication Date(Web):21 May 2012

DOI:10.1039/C2JM32033A

Two kinds of reduction and pH responsive disulfide-cross-linked poly(ethylene glycol)-polypeptide copolymers were prepared through one-step ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride (BLG NCA) or ε-benzyloxycarbonyl-L-lysine N-carboxyanhydride (ZLL NCA) and L-cystine N-carboxyanhydride (LC NCA) with amino group terminated monomethoxy poly(ethylene glycol) (mPEG-NH2) as macroinitiator. Then, the copolymers were deprotected and dispersed in phosphate buffered saline, yielding PEG-polypeptide nanogels. Doxorubicin (DOX), a model anticancer drug, was effectively loaded into nanogels via electrostatic and hydrophobic interactions. The DOX release from all DOX-loaded nanogels was accelerated in intracellular reductive and acidic conditions, which controlled by Fickian diffusion and nanogels swelling. The enhanced intracellular DOX release was observed in glutathione monoester (GSH-OEt) pretreated HeLa cells. DOX-loaded nanogels showed higher cellular proliferation inhibition towards GSH-OEt pretreated HeLa and HepG2 cells than to unpretreated or buthionine sulfoximine (BSO) pretreated cells. Hemolysis tests indicated that nanogels were hemocompatible, and the presence of nanogels could reduce the hemolysis ratio (HR) of DOX significantly. These features suggest that the nanogels can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform to construct an efficient drug delivery system for cancer therapy.

Photo-cross-linked biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Co-reporter:Changwen Zhao;Pan He;Chunsheng Xiao;Xiaoye Gao;Xuesi Chen

Journal of Applied Polymer Science 2012 Volume 123( Issue 5) pp:2923-2932

Publication Date(Web):

DOI:10.1002/app.34935

Abstract

A new strategy was developed to prepare thermo- and pH-sensitive hydrogels by the crosslinking of poly(N-isopropylacrylamide) with a biodegradable crosslinker derived from poly(L-glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli-responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Biodegradable pH-Dependent Thermo-Sensitive Hydrogels for Oral Insulin Delivery

Co-reporter:Zhe Zhang;Xiaoye Gao;Aiping Zhang;Xiaowei Wu;Li Chen;Chaoliang He;Xuesi Chen

Macromolecular Chemistry and Physics 2012 Volume 213( Issue 7) pp:713-719

Publication Date(Web):

DOI:10.1002/macp.201100604

Abstract

A series of pH-dependent thermo-sensitive hydrogels for oral insulin delivery is designed and synthesized. In contrast to normal pH- and thermo-sensitive hydrogels, the release of oral insulin from them is mainly controlled by the adjustable swelling ratios in gastric and intestinal juice with their variable pH sensitivity. The release behavior of loaded insulin depends on the swelling/shrinking transition because of the changing LCST at different pH values. The hydrogels presented are composed of PNIPAAm chains and PMAA segments and are prepared with the biodegradable acryloyl-poly(ϵ-caprolactone)-2-hydroxylethyl methacrylate as a crosslinker. The biodegradation rates of the hydrogels are directly related to their PMAA content. In vitro release of insulin from the hydrogels is investigated and the release profiles indicate that the smart hydrogels are of great promise in pH–temperature oral insulin delivery systems.

One-step preparation of reduction-responsive poly(ethylene glycol)-poly(amino acid)s nanogels as efficient intracellular drug delivery platforms

Co-reporter:Jianxun Ding, Fenghua Shi, Chunsheng Xiao, Lin Lin, Li Chen, Chaoliang He, Xiuli Zhuang and Xuesi Chen

Polymer Chemistry 2011 vol. 2(Issue 12) pp:2857-2864

Publication Date(Web):14 Oct 2011

DOI:10.1039/C1PY00360G

A series of disulfide-core-cross-linked poly(ethylene glycol)-poly(amino acid)s star copolymers were synthesized through one-step ring-opening polymerization of L-phenylalanine N-carboxyanhydride (L-Phe NCA) and L-cystine N-carboxyanhydride (L-Cys NCA) with amino group terminated poly(ethylene glycol) monomethyl ether (mPEG-NH2) as macroinitiator. The reduction-responsive PEG-poly(amino acid)s nanogels (NGs) were prepared by directly dispersing the resultant PEG-poly(amino acid)s in phosphate buffer solution at pH 7.4. Dynamic light scattering (DLS) measurements showed that the reducible NG swelled in response to 10 mM glutathione (GSH). Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the NGs. The in vitro release results revealed that the release behaviors could be adjusted by GSH concentration, and poly(amino acid)s content and composition. The intracellular DOX release results showed that enhanced intracellular DOX release occurred in GSH pretreated Henrietta Lacks (HeLa) cells. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that the NGs were biocompatible, and DOX-loaded NG showed higher cellular proliferation inhibition towards GSH pretreated HeLa cells than that of non-pretreated cells. Therefore, the NGs can efficiently deliver anticancer drugs into tumor cells and inhibit cell proliferation, rendering highly promising for targeted intracellular delivery of operative chemotherapeutic drugs in cancer therapy.

Synthesis of temperature and pH-responsive crosslinked micelles from polypeptide-based graft copolymer

Co-reporter:Changwen Zhao, Pan He, Chunsheng Xiao, Xiaoye Gao, Xiuli Zhuang, Xuesi Chen

Journal of Colloid and Interface Science 2011 Volume 359(Issue 2) pp:436-442

Publication Date(Web):15 July 2011

DOI:10.1016/j.jcis.2011.04.037

A polypeptide-based double hydrophilic graft copolymer was synthesized by the sequential grafting of poly(N-isopropylacrylamide) (PNIPAM) and 2-hydroxyethyl methacrylate (HEMA) onto poly(l-glutamic acid) (PGA) backbone. The copolymers were sensitive to both temperature and pH. The phase transition and aggregation behaviors of the graft copolymers in aqueous solutions were investigated by the turbidity measurements and dynamic laser scattering (DLS). The light transmittance decrease of the copolymers at temperature above lower critical solution temperature (LCST) was remarkably weakened at pH around 6.5 due to the coil to α helix change of PGA chain induced by pH. The copolymers can self-assembly into micelles with PNIPAM cores in the aqueous solution at pH 8.0 and 60 °C. Subsequently, polymerization of HEMA led to the facile preparation of crosslinked micelles, which were observed directly by transmission electron microscopy (TEM). The temperature controlled shrinkage behaviors of crosslinked micelles highly depended on the pH values of the solution. The crosslinked micelles aggregated at pH 5.0 due to the increased hydrophobic interactions among them induced by the protonation of PGA component. These crosslinked micelles have promising applications as intelligent drug delivery vehicles.Graphical abstractPolypeptide-based crosslinked micelle was synthesized from 2-hydroxyethyl methacrylate functionalized poly(l-glutamic acid)-graft-poly(N-isopropylacrylamide) copolymer. The crosslinked micelle exhibits temperature controlled shrinkage behaviors which highly depended on pH values.Highlights► Graft copolymer composed of poly(N-isopropylacrylamide), polypeptide and 2-hydroxyethyl methacrylate was synthesized. ► The copolymer is pH and temperature-responsive and can self-assembly into micelles. ► The copolymer micelles can be facilely crosslinked through the polymerization of 2-hydroxyethyl methacrylate. ► The introduction of polypeptide endows crosslinked micelle biodegradability.

Facile synthesis of thermo- and pH-responsive biodegradable microgels

Co-reporter:Changwen Zhao;Xiaoye Gao;Pan He;Chunsheng Xiao

Colloid and Polymer Science 2011 Volume 289( Issue 4) pp:447-451

Publication Date(Web):2011 February

DOI:10.1007/s00396-010-2365-9

A novel and facile strategy has been designed to prepare biodegradable microgels with thermo- and pH-responsive property. The microgels were synthesized by the crosslinking of N-isopropylacrylamide with vinyl groups functionalized poly(L-glutamic acid) (PGA). The resultant microgels exhibited pH-dependent phase transition behaviors in aqueous solutions and underwent abrupt lower critical solution temperature decrease when the pH was reduced below the pKa of PGA. Dynamic light scattering measurement revealed that the microgels exhibited shrinkage as the temperature increased or the pH decreased.

Synthesis of Amphiphilic Alternating Polyesters with Oligo(ethylene glycol) Side Chains and Potential Use for Sustained Release Drug Delivery

Co-reporter:Wei Wang, Jianxun Ding, Chunsheng Xiao, Zhaohui Tang, Di Li, Jie Chen, Xiuli Zhuang, and Xuesi Chen

Biomacromolecules 2011 Volume 12(Issue 7) pp:

Publication Date(Web):June 8, 2011

DOI:10.1021/bm200668n

Novel amphiphilic alternating polyesters, poly((N-phthaloyl-l-glutamic anhydride)-co-(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane) (P(PGA-co-ME2MO)), were synthesized by alternating copolymerization of PGA and ME2MO. The structures of the synthesized polyesters were characterized by 1H NMR, 13C NMR, FT-IR, and GPC analyses. Because of the presence of oligo(ethylene glycol) (OEG) side chains, the polyesters could self-assemble into thermosensitive micelles. Dynamic light scattering (DLS) showed that these micelles underwent thermoinduced size decrease without intermicellar aggregation. In vitro methyl thiazolyl tetrazolium (MTT) assay demonstrated that the polyesters were biocompatible to Henrietta Lacks (HeLa) cells, rendering their potential for drug delivery applications. Two hydrophobic drugs, rifampin and doxorubicin (DOX), were loaded into the polyester micelles and observed to be released in a zero-order sustained manner. The sustained release could be accelerated in lower pH or in the presence of proteinase K, due to the degradation of the polyester under these conditions. Remarkably, in vitro cell experiments showed that the polyester micelles accomplished fast release of DOX inside cells and higher anticancer efficacy as compared with the free DOX. With enhanced stability during circulation condition and accelerated drug release at the target sites (e.g., low pH or enzyme presence), these novel polyesters with amphiphilic structures are promising to be used in sustained release drug delivery systems.

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Co-reporter:Changwen Zhao, Xiuli Zhuang, Pan He, Chunsheng Xiao, Chaoliang He, Jingru Sun, Xuesi Chen, Xiabin Jing

Polymer 2009 50(18) pp: 4308-4316

Publication Date(Web):

DOI:10.1016/j.polymer.2009.07.010

Synthesis of Novel Thermo- and pH-Responsive Poly(L-lysine)-Based Copolymer and its Micellization in Water

Co-reporter:Changwen Zhao;Chaoliang He;Xuesi Chen;Xiabin Jing

Macromolecular Rapid Communications 2008 Volume 29( Issue 22) pp:

Publication Date(Web):

DOI:10.1002/marc.200800494

Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy

Co-reporter:Jianxun Ding, Fenghua Shi, Di Li, Li Chen, Xiuli Zhuang and Xuesi Chen