Affibody-Functionalized Elastin-like Peptide–Drug Conjugate Nanomicelle for Targeted Ovarian Cancer Therapy

Recombinant elastin-like polypeptides (ELPs) have emerged as an attractive nanoplatform for drug delivery due to their tunable genetically encoded sequence, biocompatibility, and stimuli-responsive self-assembly behaviors. Here, we designed and biosynthesized an HER2 (human epidermal growth factor receptor 2)-targeted affibody-ELP fusion protein (Z-ELP), which was subsequently conjugated with monomethyl auristatin E (MMAE) to build a protein-drug conjugate (Z-ELP-M). Due to its thermal response, Z-ELP-M can immediately self-assemble into a nanomicelle at physiological temperature. Benefiting from its active targeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization and deep tumor penetration <i>in vitro</i>. Moreover, Z-ELP-M shows excellent tumor targeting and superior antitumor efficacy in HER2-positive ovarian cancer, demonstrating a relative tumor growth inhibition of 104.6%. These findings suggest that an affibody-functionalized elastin-like peptide-drug conjugate nanomicelle is an efficient strategy to improve antitumor efficacy and biosafety in cancer therapy.