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
• 来源期刊: 纳微快报（英文版）
• 年，卷（期）: 2022,（2）
• 页码范围: 190-205
• 页数: 16页
• 语种: 英文

摘要

Affibody molecules are small non-immunoglobulin affinity proteins,which can pre-cisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seri-ously 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 con-jugate of ZHER2:342-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 mm3) and large established tumors (exceed 500 mm3).The relative tumor proliferation inhibition ratio reaches 99.8％ for both models.