Targeting Melanoma-Specific Tyrosinase: Cyclic Peptide Disrupts Actin Dynamics for Precision Apoptosis Induction

TL;DR

This study introduces a cyclic peptide that selectively targets melanoma cells by exploiting tyrosinase overexpression, disrupting actin dynamics to induce apoptosis with high specificity and minimal toxicity.

Contribution

The paper presents a novel enzyme-responsive cyclic peptide that selectively induces apoptosis in melanoma cells by disrupting actin, offering a potential targeted therapy without external drug payloads.

Findings

High selectivity for melanoma cells

Effective tumor suppression in murine models

Minimal systemic toxicity observed

Abstract

Melanoma is an aggressive and highly metastatic cancer that exhibits stubborn resistance to conventional therapies, highlighting the need for novel treatments. Existing therapeutic strategies often suffer from systemic toxicity, poor efficacy and fast-gained drug resistance. In this study, we designed a cyclic peptide system (c-RGDKYQ) that takes the advantage of the overexpression of tyrosinase in melanoma cells to trigger enzyme-mediated oxidation and self-assembly. The assembled peptide nanostructures can selectively disrupt the actin cytoskeleton, impairing cancer cellular functions, e.g., motility, adhesion, and proliferation, ultimately leading to apoptosis. This approach does not rely on external drug payloads or complex delivery mechanisms. c-RGDKYQ exhibits high selectivity for melanoma cells, strongly suppressing tumor growth in a murine model with minimal systemic toxicity. Our findings illuminate that, through targeting tyrosinase, c-RGDKYQ may be an enzyme-responsive alternative to conventional treatments for melanoma.