Intracellular redox dyshomeostasis promoted by tumor microenvironment (TME) modulation has become an appealing therapeutic target for cancer management. Herein, a dual plasmonic Au/SF@Cu2-xS nanoreactor (abbreviation as ASC) is elaborately developed by covalent immobilization of sulfur defective Cu2-xS nanodots onto the surface of silk fibroin (SF)-capped Au nanoparticles. Tumor hypoxia can be effectively alleviated by ASC-mediated local oxygenation, owing to the newfound catalase-mimic activity of Cu2-xS. The semiconductor of Cu2-xS with narrow bandgap energy of 2.54 eV enables a more rapid dissociation of electron-hole (e-/h+) pair for a promoted US-triggered singlet oxygen (1O2) generation, in the presence of Au as electron scavenger. Moreover, Cu2-xS is devote to Fenton-like reaction to catalyze H2O2 into ·OH under mild acidity and simultaneously deplete glutathione to aggravate intracellular oxidative stress. In another aspect, Au nanoparticles with glucose oxidase-mimic activity consumes intrinsic glucose, which contributes to a higher degree of oxidative damage and energy exhaustion of cancer cells. Importantly, such tumor starvation and 1O2 yield can be enhanced by Cu2-xS-catalyzed O2 self-replenishment in H2O2-rich TME. ASC-initiated M1 macrophage activation and therapy-triggered immunogenetic cell death (ICD) favors the systematic tumor elimination by eliciting antitumor immunity. This study undoubtedly enriches the rational design of SF-based nanocatalysts for medical utilizations.
Keywords: Nano-sonosensitizer; Redox homeostasis; Silk fibroin; Tumor microenvironment; Tumor starvation.
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