Abstract
Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO(2) nanodots-engineered thermosensitive chitosan hydrogel (CuO(2)-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO(2) nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu(2+), the CuO(2) nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H(2)O(2) under acidic tumor microenvironment. Simultaneously, the CuO(2) nanodots with a narrow bandgap (2.29 eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen ((1)O(2)) could be boosted by the O(2) generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.