Catalytic MnWO4 Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast Cancer

Nanomedicine-based synergy of chemodynamic therapy (CDT) and radiotherapy (RT) modulated by tumor microenvironment enables rapid tumor ablation, which holds great hope for the refractory and recurrent cancers, such as triple negative breast cancer (TNBC). The clinical translation of hafnium oxide (HfO₂), commercially named as NBTXR3, has aroused new research focus on single-component inorganic nanomedicines as clinical candidates. Herein, the single-component MnWO₄ is first reported as a new kind of Fenton-like agent yet radiosensitizer for TNBC treatment undergoing the synergistic CDT/RT mechanism. MnWO₄ nanorods are synthesized via a simple one-pot hydrothermal method and then undergo a layer-by-layer PEGylation to obtain bioavailable MnWO₄-PEG (MWP). MWP-based Fenton-like reaction efficacy depends on reaction time, temperatures, pH values, and MWP concentrations. Mn-triggered chemodynamic effect delays RT-induced DNA damage repair and sorts cell cycles distribution toward radiosensitive phases, while W-mediated radiosensitization improves the tumoral H₂O₂ overexpression to enhance CDT, remarkably amplifying of the intracellular oxidative stress to boost 4T1 cell apoptosis. In vitro and in vivo evaluations further demonstrate the effectiveness and biosafety of MWP-based synergistic therapy. Considering the potential magnetic resonance and computed tomography imaging capabilities, MWP can be expected as an intelligent cancer theranostics for imaging-guided cancer therapy in clinic in the future.