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

Recombinant\nelastin-like polypeptides (ELPs) have emerged as an\nattractive nanoplatform for drug delivery due to their tunable genetically\nencoded sequence, biocompatibility, and stimuli-responsive self-assembly\nbehaviors. Here, we designed and biosynthesized an HER2 (human epidermal\ngrowth factor receptor 2)-targeted affibody–ELP fusion protein\n(Z-ELP), which was subsequently conjugated with monomethyl auristatin\nE (MMAE) to build a protein–drug conjugate (Z-ELP-M). Due to\nits thermal response, Z-ELP-M can immediately self-assemble into a\nnanomicelle at physiological temperature. Benefiting from its active\ntargeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization\nand deep tumor penetration <i>in vitro</i>. Moreover, Z-ELP-M\nshows excellent tumor targeting and superior antitumor efficacy in\nHER2-positive ovarian cancer, demonstrating a relative tumor growth\ninhibition of 104.6%. These findings suggest that an affibody-functionalized\nelastin-like peptide–drug conjugate nanomicelle is an efficient\nstrategy to improve antitumor efficacy and biosafety in cancer therapy.