Dual Fenton Catalytic Nanoreactor for Integrative Type-I and Type-II Photodynamic Therapy against Hypoxic Cancer Cells

Tumor hypoxia is a noteworthy impediment to effective photodynamic therapy (PDT), as it would sharply weaken the effectiveness of oxygen-dependent PDT. To enable effective PDT in both hypoxia as well as normoxia circumstances, here, we report a multifunctional nanoreactor (C₃N₄/MnO₂ NPs), which guarantees effective type-II PDT (oxygen-dependent) in hypoxia by in situ oxygen generation via the Fenton reaction. In addition, the C₃N₄/MnO₂ NPs can also be used for oxygen-independent type-I PDT by evolving the cytotoxic hydroxyl radical to reduce reliance on intracellular oxygen content. In vitro cytotoxicity assays made evident that the C₃N₄/MnO₂ NPs exhibit a much higher cancer-cell-killing ability than C₃N₄ NPs not only in normoxia but also in hypoxic circumstances. The smart integration of type-I and type-II PDT into the therapeutic nanoplatform enables effective PDT even though intracellular oxygen is not satisfactory.