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 

作者机构：School of Chemical EngineeringSichuan UniversityNo.24 South Section 1Yihuan RoadChengdu 610065China National Engineering Research Center for BiomaterialsSichuan UniversityNo.29 Wangjiang RoadChengdu 610064China 

出 版 物：《Regenerative Biomaterials》 (再生生物材料（英文版）)

年 卷 期：2020年第7卷第4期

页      面：359-369页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 

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). 

主　　题：good stability,π-conjugated moieties active-targeting,redox-activated 

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.