Hydrogen Peroxide Responsive Hafnium-Based Nanomaterials for Enhanced Tumor Radiosensitization

Overcoming the dual hurdles of intrinsic tumor hypoxia and radioresistance remains a formidable challenge in solid tumor therapy. Herein, we report the rational design of an intelligent Pt@Hf MOF nanotherapy platform that orchestrates physical and chemical radiosensitization. By harnessing the synergistic effect of dual high-Z elements (Pt, Z = 78; Hf, Z = 72), this system significantly enhances X-ray energy deposition for physical dose amplification. Crucially, the nanocomposite exhibits dual-enzyme activities: it alleviates hypoxia via the catalase-like activity of endogenous H₂O₂, thereby reversing radioresistance; simultaneously, it catalyzes H₂O₂ to generate highly toxic hydroxyl radicals, inducing severe oxidative stress and irreparable DNA double-strand breaks. Both systematic in vitro and in vivo studies demonstrate that this strategy effectively inhibits tumor proliferation and induces apoptosis. Notably, in a triple-negative breast cancer model, this platform remodels the hypoxic microenvironment, achieving remarkable tumor suppression. This work presents a paradigm of precision radiotherapy that integrates microenvironment modulation with multimodal killing, offering a robust strategy against refractory malignancies.