A robust Au@CuS nanoreactor assembled by silk fibroin for enhanced intratumoral glucose depletion and redox dyshomeostasis.

Intracellular redox dyshomeostasis promoted by tumor microenvironment (TME) modulation has become an appealing therapeutic target for cancer management. Herein, a dual plasmonic Au/SF@CuS nanoreactor (abbreviation as ASC) is elaborately developed by covalent immobilization of sulfur defective CuS 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 CuS. The semiconductor of CuS 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 (O) generation, in the presence of Au as electron scavenger. Moreover, CuS is devote to Fenton-like reaction to catalyze HO 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 O yield can be enhanced by CuS-catalyzed O self-replenishment in HO-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.