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

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 (Z_{PDGFRβ: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 Z_{PDGFRβ:09591}-MMAE affibody-drug conjugate nanomedicine (Z_{PDGFRβ:09591}-M ADCN) resulted in enhanced pharmacokinetics, improved drug accumulation, and promoted biosecurity performance than those of free drugs. As a result, Z_{PDGFRβ: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 Z_{PDGFRβ:09591}-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.