Smart phase-change CuS@Vk3@LA nanoplatform enables tumor-selective, synergistic chemodynamic and photothermal therapy

Ovarian cancer therapy remains limited by high recurrence and unsatisfactory responses to current treatments. Here, we developed a multifunctional nanoplatform (CuS@Vk3@LA) that integrates photothermal therapy (PTT), chemodynamic therapy (CDT), and near-infrared (NIR)-controlled drug release. The hollow CuS core serves as both a NIR absorber and a Fenton-like catalyst, enabling simultaneous heat generation and hydroxyl radical production. Uniquely, vitamin K3 (Vk3) was incorporated to enhance endogenous H₂O₂ levels through NQO1-mediated redox cycling, thereby overcoming the substrate shortage that restricts conventional CDT. To prevent premature leakage, lauric acid (LA) was introduced as a thermosensitive phase-change shell, which melts under mild hyperthermia to trigger on-demand release. This rational design establishes a dual oxidative-stress mechanism-ROS amplification and GSH depletion-resulting in synergistic tumor cell killing. Systematic evaluations demonstrated excellent colloidal stability, biocompatibility, and tumor-selective accumulation. In vivo, CuS@Vk3@LA achieved pronounced tumor growth inhibition with minimal systemic toxicity. Collectively, this study provides a precise and safe nanotherapeutic strategy that combines catalytic amplification with photothermal activation, showing strong translational potential for ovarian cancer treatment.