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Vol. 14 (2022)

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

https://doi.org/10.1007/s40820-021-00762-9
Xuelin Xia
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Xiaoyuan Yang
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Wei Huang
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Xiaoxia Xia
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Deyue Yan
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China

Corresponding Author: Deyue Yan

dyyan@sjtu.edu.cn

Nano-Micro Letters, Vol. 14 (2022), Article Number: 33

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 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.


Highlights:


1 The nanoagent of affibody-drug conjugate made of ZHER2:342 and MMAE was successfully fabricated through molecular self-assembly of the conjugate in aqueous solution for targeted cancer therapy, which is recorded as Z-M ADCN for short.
2 Z-M ADCN shows extraordinary anticancer ability in HER2-positive ovary and breast tumor models with good biosecurity, that nearly eradicated both small solid tumors (about 100  mm3) and large tumors (exceed 500  mm3).

Keywords

Molecular self-assembly Affibody-drug conjugate Nanoagent Targeted cancer therapy
Xia, Xuelin, Xiaoyuan Yang, Wei Huang, Xiaoxia Xia, and Deyue Yan. 2021. “Self-Assembled Nanomicelles of Affibody-Drug Conjugate With Excellent Therapeutic Property to Cure Ovary and Breast Cancers”. Nano-Micro Letters 14 (December):33. https://doi.org/10.1007/s40820-021-00762-9.
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