Self-Assembled Nanomicelles of Affibody-Drug Conjugate with Excellent Therapeutic Property to Cure Ovary and Breast Cancers  

作　　者：Xuelin Xia Xiaoyuan Yang Wei Huang Xiaoxia Xia Deyue Yan 

机构地区：[1]School of Chemistry and Chemical Engineering,Frontiers Science Center for Transformative Molecules,Shanghai Jiao Tong University,Shanghai 200240,People’s Republic of China [2]State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,People’s Republic of China

出　　处：《Nano-Micro Letters》2022年第2期190-205,共16页纳微快报（英文版）

基　　金：Research and Development Plan of China(No.2016YFA0201500,2020YFA0907702);National Facility for Translational Medi-cine(Shanghai)(No.TMST-2020-001)for financial support.

摘　　要：Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seriously limited their application in drug targeted delivery for cancer therapy.Here an amphiphilic affibody-drug conjugate is self-assembled into nanomicelles to prolong circulation time for targeted cancer therapy.As an example of the concept,the nanoagent was prepared through molecular self-assembly of the amphiphilic conjugate of Z_(HHR2:342)-Cys with auristatin E derivate,where the affibody used is capable of binding to the human epidermal growth factor receptor 2(HER2).Such a nanodrug not only increased the blood circulation time,but also enhanced the tumor targeting capacity(abundant affibody arms on the nanoagent surface) and the drug accumulation in tumor.As a result,this affibody-based nanoagent showed excellent antitumor activity in vivo to HER2-positive ovary and breast tumor models,which nearly eradicated both small solid tumors(about 100 mm^(3)) and large established tumors(exceed 500 mm^(3)).The relative tumor proliferation inhibition ratio reaches 99.8% for both models.

关 键 词：Molecular self-assembly Affibody-drug conjugate Nanoagent Targeted cancer therapy 

分 类 号：R730.5[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]