Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

作     者：PANG Yan 1,LIU JinYao 1,SU Yue 1,ZHU BangShang 2,HUANG Wei 1,ZHOU YongFeng 1,ZHU XinYuan 1,2 & YAN DeYue 1 1 School of Chemistry and Chemical Engineering,State Key Laboratory of Metal Matrix Composites,Shanghai Jiao Tong University,Shanghai 200240,China 2 Instrumental Analysis Center,Shanghai Jiao Tong University,Shanghai 200240,China 

作者机构：School of Chemistry and Chemical Engineering State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong University Shanghai China Instrumental Analysis Center Shanghai Jiao Tong University Shanghai China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2010年第53卷第12期

页      面：2497-2508页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 0703[理学-化学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：sponsored by the National Natural Science Foundation of China(21025417,20974062,50773037 & 50633010) National Basic Research Program 2007CB808000 the Fok Ying Tung Education Foundation(111048) Shuguang Program(08SG14) Shanghai Leading Academic Discipline Project(Project Number:B202) 

主　　题：hyperbranched polymer unimolecular micelle drug delivery 

摘      要：A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn H40 core,poly(L-lactide) (PLA) inner-shell,and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by *** obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR),Fourier transform infrared (FTIR),gel permeation chromatography (GPC),differential scanning calorimeter (DSC),and thermal gravimetric analysis (TGA).Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 ***,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide *** a hydrophobic anticancer model drug,doxorubicin (DOX) was encapsulated into these reductive unimolecular *** vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug *** cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living *** tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free *** of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.