Injectable redox and light responsive MnO₂ hybrid hydrogel for simultaneous melanoma therapy and multidrug-resistant bacteria-infected wound healing.

Abstract

The recurrence of cutaneous cancer and multidrug-resistant (MDR) bacteria infected-wound healing after surgical excision remains a great challenge for both clinic and research. In this study, we developed an injectable redox and light responsive bio-inspired MnO₂ hybrid (BMH) hydrogel for effective melanoma photothermo-chemotherapy and MDR bacteria infected-wound healing. The BMH hydrogel was ingeniously fabricated via non-covalent self-assembly and MnO₂ nanosheets mediated covalent oxidative polymerization of the catechol functionalized chitosan for the first time. The BMH hydrogel displayed excellent shear-thinning, injectable, adhesive, redox/light responsive and contact-active antibacterial capabilities. Remarkably, our rationally designed BMH hydrogel could alleviate the hypoxic tumor microenvironment (TME) by decomposing the endogenous H₂O₂ into O₂, and simultaneously release anticancer drug DOX. Increasing the local availability of O₂ enhanced the cytotoxicity of DOX against melanoma in a highly site-specific manner. By further combining with a spatiotemporal controllable photothermal hyperthermia, we demonstrated a near-complete tumor suppression both in vitro (98.6%) and large solid tumors in vivo (96.2%). Moreover, BMH hydrogel could significantly promote the MDR-infected wound healing in vivo by efficiently eradicating bacterial invasion and perpetually ameliorating the oxidative and inflammatory wound microenvironment. Collectively, BMH hydrogel indicated great therapeutic potentials for both cancer therapy and tissue engineering.