Achieving apoptosis/cuproptosis co-activated synergistic anti-tumor therapy by charges transport engineering

Abstract

Nanocatalysts show great promise in nanomedicine due to their unique catalytic activities. However, the rapid recombination of excited electrons and holes leads to low efficacy of nanocatalytic therapy. Herein, ultrasmall S-Scheme heterojunction MoC/CuFeO_x nanoparticles (MCFO NPs) with specific charge transport route are rationally designed and engineered for efficient apoptosis/cuproptosis co-activated nanocatalytic therapy. Thermal analysis revealed two steps of S-Scheme heterojunction formation: adsorption and internal structure change. In this structure, the staggered energy levels and band bending enhance the separation of photogenerated electrons and holes, improving redox capacity and catalytic activity, mediating O₂ production, regulating the hypoxic tumor microenvironment, increasing reactive oxygen species, and inducing apoptosis. Additionally, due to excessive copper, the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase and disruption of tricarboxylic acid cycle are caused to evoke cuproptosis. This work proposes a feasible strategy to enhance the nanocatalytic therapeutic efficacy through charge transport engineering, thereby mediating apoptosis/cuproptosis co-activated synergistic anti-tumor therapy.