Hollow copper sulfide nanomedicines functionalized with metal polyphenol network for self-augmenting chemodynamic and...

Chemodynamic therapy (CDT) holds promise for tumor treatment but is limited by insufficient endogenous hydrogen peroxide (H₂O₂) and slow Fe³⁺/Fe²⁺ cycling in the tumor microenvironment (TME). Herein, we report a self-augmenting nanoplatform (CPT@HCuS-TF) by loading camptothecin (CPT) into hollow copper sulfide (HCuS) nanoparticles and sealing with an Fe³⁺-containing polyphenol network (MPN). Under acidic TME and near-infrared (NIR) irradiation, the MPN shell degrades to release Fe³⁺, CPT is liberated to amplify endogenous H₂O₂ levels, and HCuS acts as a catalyst to accelerate the reduction of Fe³⁺ to Fe²⁺, thereby overcoming the rate-limiting step of the Fenton reaction and boosting hydroxyl radical (•OH) generation. Meanwhile, HCuS-mediated photothermal therapy (PTT) further enhances CDT efficacy. This synergistic strategy integrates self-supplied H₂O₂, accelerated iron redox cycling, and photothermal effects, achieving efficient antitumor activity in both in vitro and in vivo model, offering a robust paradigm for self-enhancing CDT-based combination therapy.