Self-Assembled Nanomicelles of Affibody-Drug Conjugate with Excellent Therapeutic Property to Cure Ovary and Breast Cancers
Xuelin Xia, Xiaoyuan Yang, Wei Huang, Xiao‐Xia Xia, Deyue Yan
Abstract
Abstract Affibody molecules are small non-immunoglobulin 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 HER2:342 -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.