ROS-responsive multifunctional DCS-based micelle hydrogel for simultaneously inhibiting post-resection melanoma recurrence and promoting wound healing

Abstract

Delayed healing of post-resection melanoma wounds is prone to induce tumor recurrence. Therefore, postoperative wound management for tumor resection needs to concurrently address anti-cancer activity and wound healing promotion. In this study, a multifunctional micelle hydrogel (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which was co-loaded with apigenin and BMS-202, into a dodecyl-modified chitosan (DCS)-based hydrogel via Schiff base linkages and hydrogen bonding interactions for post-resection melanoma therapy. This micelle hydrogel enabled ROS-triggered drug release, thereby minimizing systemic toxicity. More importantly, the released apigenin exerted selective cytotoxicity against tumor cells and bacteria while inducing immunogenic cell death (ICD). When combined with co-released BMS-202, the formulation enhanced anti-tumor efficacy without harming normal tissue cells. Moreover, AB@MH was fabricated via a straightforward, crosslinker-free method, ensuring excellent biocompatibility and effective wound healing promotion. In the melanoma resection model, the AB@MH group markedly suppressed tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy.