In Situ Photocatalysis of TiO-Porphyrin-Encapsulated Nanosystem for Highly Efficient Oxidative Damage against Hypoxic Tumors.

Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze H2O and tumor-overexpressed H2O2, in situ generating sufficient ROS. TiOP can photosplit water to produce ·OH radical, H2O2, and O2. Generated O2 not only conquers the hypoxia of tumor environment but also can be further excited by TiOP to 1O2 for killing tumor cells. Density functional theory calculations indicate that high energy in excited state (S1) of TiOP and narrow gap energy between S1 and the triplet excited state (Tn) might contribute to the efficient photocatalytic action. Moreover, the generated and overexpressed H2O2 in tumors can also be photocatalyzed to generate 1O2 especially in acid condition, helpful to specific anticancer effect while harmless to normal tissues. This research might pave a new way to bypass the hypoxia-triggered problem for cancer therapy.