Development of a hydrogen peroxide-responsive and oxygen-carrying nanoemulsion for photodynamic therapy against hypoxic tumors using phase inversion composition method

Photodynamic therapy (PDT) has become an attractive tumor treatment modality because of its noninvasive feature and low side effects. However, extreme hypoxia inside solid tumors severely impedes PDT therapeutic outcome. To overcome this obstacle, various strategies have been developed recently. Among them, in situ oxygen generation, which relies on the decomposition of tumor endogenous H2O2, and oxygen delivery tactic using high oxygen loading capacity of hemoglobin or perfluorocarbons, have been widely studied. The in situ oxygen generation strategy has high specificity to tumors, but its oxygen-generating efficiency is limited by the intrinsically low tumor H2O2 level. In contrast, the oxygen delivery approach holds advantage of high oxygen loading efficiency, nevertheless lacks tumor specificity. In this work, we prepared a nanoemulsion system containing H2O2-responsive catalase, highly efficient oxygen carrier perfluoropolyether (PFPE), and a near-infrared (NIR) light activatable photosensitizer IR780, to combine the high tumor specificity of the in situ oxygen generation strategy and the high efficiency of the oxygen delivery strategy. This concisely prepared nanoplatform exhibited enhanced and H2O2-controllable production of singlet oxygen under light excitation, satisfactory cytocompatibility, and ability to kill cancer cells under NIR light excitation. This highlights the potential of this novel nanoplatform for highly efficient and selective NIR light mediated PDT against hypoxic tumors. This research provides new insight into the design of intelligent nanoplatform for relieving tumor hypoxia and enhancing the oxygen-dependent PDT effects in hypoxic tumors.