H2O2 self-supplying cascade nanocomposite for photothermally enhanced chemodynamic therapy

Chemodynamic therapy (CDT) shows significant promise for cancer treatment. However, the low endogenous hydrogen peroxide (H 2 O 2 ) levels within tumors frequently constrain the efficacy of CDT. To address this limitation, we developed a H 2 O 2 -self-supplying cascade nanocomposite, MgO 2 @CuFe 2 O 4 @PEG (designated MCuFeP), capable of generating H 2 O 2   in situ   through MgO 2 decomposition in the tumor microenvironment. The CuFe 2 O 4 converted the self-supplied H 2 O 2 into cytotoxic reactive oxygen species (ROS) via Fenton and Fenton-like reactions. Furthermore, MCuFeP exhibited pronounced photothermal effects under near-infrared (NIR) irradiation, directly ablating tumor cells and significantly accelerating the catalytic reaction. In vitro studies confirmed that MCuFeP generated substantial heat and ROS upon NIR irradiation. Notably, the nanocomposite demonstrated cytocompatibility with healthy L929 cells while selectively inducing death in cancerous 4 T1 cells and the effect was enhanced by NIR irradiation. In the subcutaneous syngeneic 4 T1 tumor model mice, MCuFeP + NIR inhibited tumor growth over the 14-day treatment period. Histopathological analysis showed damage to tumor cells without significant toxicity to major organs, and hemocompatibility assessment confirmed favorable blood compatibility. Collectively, these results demonstrate that MCuFeP is a highly promising nanocomposite for the development of novel combinatorial cancer therapies.