A copper sulfide/glucose oxidase/elesclomol nanoplatform for photothermal enhanced copper-induced toxicity/chemodynamic tumor combination therapy

Despite being more effective than single treatments for cancer, combination therapy poses a challenge in integrating multiple modalities. In this study, we propose a nanoplatform (CuS@GOx@ES) that integrates chemodynamic therapy (CDT), starvation therapy (ST), photothermal therapy (PTT), and copper-induced toxicity for enhanced cancer treatment. CuS nanoparticles, with their large surface area, are ideal for CDT, while glucose oxidase (GOx) depletes tumor glucose for ST and catalyzes H₂O₂ production for a Fenton-like reaction. The glucose depletion generates gluconic acid, which accelerates CuS degradation and Cu²⁺ release, enhancing both CDT and copper-induced toxicity. CuS also exhibits excellent photothermal properties and enhances PTT under 808 nm NIR irradiation. The increased temperature further amplifies the effects of CDT and copper-induced toxicity. Additionally, CuS serves as an exogenous source of copper, releasing Cu²⁺ into the tumor microenvironment (TME), where it binds to the copper ion carrier ES for targeted delivery to tumor cells, inducing copper-induced toxicity and tumor cell death. The CuS@GOx@ES nanoplatform effectively combines CDT, PTT, ST, and copper-induced toxicity, creating a synergistic effect where the treatments enhance each other to achieve superior therapeutic outcomes.