Targeted pH-responsive polyion complex micelle for controlled intracellular drug delivery  

作　　者：Pan Zheng Yang Liu Jinjin Chen Weiguo Xu Gao Li Jianxun Ding 

机构地区：[1]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences.Changchun 130022,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China

出　　处：《Chinese Chemical Letters》2020年第5期1178-1182,共5页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(Nos.51973216,51873207,51833010,51703225,51673190,51673187,51603204 and 51520105004);the Science and Technology Development Program of Jilin Province(No.20190201068JC);the National Key Research and Development Program of China(No.2016YFC1100701);the Youth Talents Promotion Project of Jilin Province(No.181909);the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。

摘　　要：Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.

关 键 词：POLYPEPTIDE TARGETING pH-responsiveness Intracellular drug delivery Cancer therapy 

分 类 号：TQ460.4[化学工程—制药化工]