High-drug-loading capacity of redox-activated biodegradable nanoplatform for active targeted delivery of chemotherapeutic drugs  

作　　者：Hai Zhang Jianqin Yan Heng Mei Shengsheng Cai Sai Li Furong Cheng Jun Cao Bin He 

机构地区：[1]School of Chemical Engineering,Sichuan University,No.24 South Section 1,Yihuan Road,Chengdu 610065,China [2]National Engineering Research Center for Biomaterials,Sichuan University,No.29 Wangjiang Road,Chengdu 610064,China

出　　处：《Regenerative Biomaterials》2020年第4期359-369,共11页再生生物材料（英文版）

基　　金：supported by the Natural Science Foundation of China(Grant No.51973135);National Key Research and Development Program of China(Grant Nos.2018YFC1106103,2017YFB0702600,2017YFB0702603);Science and Technology Foundation of Sichuan Province(Grant No.2018RZ0044).

摘　　要：Challenges associated with low-drug-loading capacity,lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy.Herein,we constructed active-targeting,redox-activated polymeric micelles(HPGssML)selfassembled aptamer-decorated,amphiphilic biodegradable poly(benzyl malolactonate-co-e-caprolactone)copolymer with disulfide linkage and p-conjugated moieties.HPGssML with a homogenous spherical shape and nanosized diameter(-150 nm)formed a low critical micellar concentration(10^-3mg/mL),suggesting good stability of polymeric micelles.The anticancer drug,doxorubicin(DOX),can be efficiently loaded into the core of micelles with high-drug-loading content via strong π-π interaction,which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles.The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment.Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells.An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration(IC50)of DOX-loaded HPGssML was two times lower than that of the control group,demonstrating improved antitumor efficacy.Therefore,the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.

关 键 词：good stability π-conjugated moieties active-targeting redox-activated 

分 类 号：R730.53[医药卫生—肿瘤]