Defective Engineered Metal–Organic Frameworks for Tumor Cell-Specific Combined Therapy

Tumor-specific combination therapies have emerged as highly promising strategies in the realm of cancer theranostics, offering the potential for improving therapeutic efficacy. Herein, we developed a hyaluronic-acid-functionalized defective metal-organic framework (Fe-UiO@HA), which serves as an integrated nanoplatform for synergistic cancer treatment by combining phototherapy and chemodynamic therapy. Fe-UiO exhibits the glutathione oxidase (GSHOx) and Fenton-like catalytic activity, which effectively depletes intracellular GSH and catalyzes the decomposition of H₂O₂, consequently elevating intracellular reactive oxygen species levels in cancer cells. Meanwhile, Fe-UiO exhibits a significantly improved separation and migration efficiency of photogenerated electron-hole pairs, leading to remarkable photocatalytic activity. Importantly, the surface modification with hyaluronic acid (HA) promotes the accumulation and uptake of Fe-UiO via CD44-overexpressing tumor cells, thereby achieving a more satisfactory therapeutic efficacy. In brief, these results demonstrate that the "all-in-one" nanotherapeutic platform, which integrates phototherapy and chemodynamic therapy capabilities, exhibits synergistic effects that significantly enhance the therapeutic efficacy of cancer treatment.