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

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

机构地区：[1]School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Nano Research》2023年第4期5256-5264,共9页纳米研究（英文版）

基　　金：supported by the National Key Research and Development Plan of China(No.2020YFA0907702);the National Facility for Translational Medicine(Shanghai)(No.TMST-2020-001).

摘　　要：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 receptorβ)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 mm^(3))or large established tumors(~500 mm^(3)),indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.

关 键 词：olecular self-assembly ZPDGFRβ:09591 affibody monomethyl auristatin E(MMAE) nanodrug targeted delivery 

分 类 号：R735.34[医药卫生—肿瘤]