A pH-responsive ZnO2@ZIF-8/TCPP nanoplatform with self-supplied oxygen for hypoxia-relieved photodynamic therapy

Tumor hypoxia limits type-II photodynamic therapy (PDT) by restricting oxygen-dependent singlet oxygen production during irradiation. Here, we developed a pH-responsive ZnO 2 @ZIF-8/TCPP nanoplatform (PZZT) that integrates an acid-activated oxygen-generating core (ZnO 2 ), a ZIF-8 gatekeeper shell, and the photosensitizer TCPP, aiming to enhance PDT under hypoxic conditions. Under mildly acidic conditions, PZZT showed improved oxygen generation and enhanced DPBF consumption upon 660 nm irradiation, indicating elevated ¹O₂ production. In 4T1 cells, PZZT + laser induced stronger intracellular ROS signals and greater phototoxicity than free TCPP or control formulations. In 4T1 tumor-bearing mice, PZZT + laser achieved the most significant tumor growth inhibition without obvious systemic toxicity. Overall, PZZT provides a practical pH-activated self-oxygen-supplying strategy to improve PDT efficacy.