title: New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release.
abstract: For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential.
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Yang
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: ceszhlm@mail.sysu.edu.cn.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D057930:Click Chemistry; D003911:Dextrans / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D008727:Methotrexate / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D006020:Glycopeptides; D008823:Micelles; D014867:Water; D004229:Dithiothreitol; D008727:Methotrexate
keywords: Disulfide bond; Drug release; Glycopolypeptide; Reduction-sensitive micelles