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Research Article

Highly efficient tumor-targeted nanomedicine assembled from affibody-drug conjugate for colorectal cancer therapy

Xiaoyuan Yang1Xuelin Xia1Wei Huang1Xiaoxia Xia2( )Deyue Yan1( )
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
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Graphical Abstract

A nanomedicine (ZPDGFRβ:09591-M affibody-drug conjugate nanomedicine (ADCN)) self-assembled from the conjugate of affibody ZPDGFRβ:09591 with monomethyl auristatin E (MMAE) is prepared for targeted colorectal cancer therapy. ZPDGFRβ:09591-M ADCN shows excellent antitumor efficacy and good biosafety in platelet-derived growth factor receptor β (PDGFRβ)-positive tumor models.

Abstract

Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors. Owing to the simple framework, affibody is flexible for modification with payload, but the relatively low molecular weight of this construction simultaneously results in short half-life time which hinders its application in cancer therapy. In this work, we prepared a nanomedicine self-assembled from the conjugate of affibody (ZPDGFRβ:09591, PDGFRβ: platelet-derived growth factor receptor β) with monomethyl auristatin E (MMAE) through cathepsin B cleavable dipeptide linker for targeted colorectal cancer therapy. The nanoscale characteristics of ZPDGFRβ:09591-MMAE affibody-drug conjugate nanomedicine (ZPDGFRβ:09591-M ADCN) resulted in enhanced pharmacokinetics, improved drug accumulation, and promoted biosecurity performance than those of free drugs. As a result, ZPDGFRβ:09591-M ADCN exhibited excellent antitumor efficacy with tumor inhibition rates (TIR) over 99.0% in PDGFRβ-positive tumor models with small solid tumors (~ 150 mm3) or large established tumors (~ 500 mm3), indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.

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Nano Research
Pages 5256-5264
Cite this article:
Yang X, Xia X, Huang W, et al. Highly efficient tumor-targeted nanomedicine assembled from affibody-drug conjugate for colorectal cancer therapy. Nano Research, 2023, 16(4): 5256-5264. https://doi.org/10.1007/s12274-022-5183-8
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Received: 07 August 2022
Revised: 08 October 2022
Accepted: 10 October 2022
Published: 31 December 2022
© Tsinghua University Press 2022
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