Azo Initiator Loaded Black Mesoporous Titania with Multiple Optical Energy Conversion for Synergetic Photo-Thermal-Dynamic Therapy

To date, the limited light conversion ability and the oxygen-dependent therapeutic process of most photosensitizers make it difficult to achieve satisfactory therapeutic effects in the complex tumor microenvironment, especially the anoxic environment. Herein, the black mesoporous titania (BMT) with large pore size (∼8 nm) is synthesized as a new-style carrier for radical generator drug (AIBI) loading. The BMT as a light transducer can convert near-infrared (NIR) light energy into thermal energy and chemical energy (•OH), contributing to photothermal therapy (PTT) and photodynamic therapy (PDT), respectively. More importantly, AIBI would be thermally decomposed into alkyl radicals (•R) for thermodynamic therapy (TDT). The high concentration of free radicals produced by BMT@AIBI NCs resulted in double-strand breaks (DSBs) of DNA and finally induced cancer cell apoptosis. Since the generation of radicals is unrelated to oxygen, the BMT@AIBI NCs with NIR irradiation presented excellent in vitro and in vivo anticancer results under hypoxic conditions. The reported NIR-induced platform based on BMT@AIBI NCs, which could perform triple energy-conversion processes including light energy to thermal energy, to chemical energy, and to thermal energy then to chemical energy, realizes synergetic photo-thermal-dynamic therapy (PTT, PDT, and TDT) to overcome the problem of tumor hypoxia for enhanced anticancer effects.