Abstract
Titania semiconductors can be activated by external physical triggers to produce electrons (e(-)) and holes (h(+)) pairs from the energy-band structure and subsequently induce the generation of reactive oxygen species for killing cancer cells, but the traditional ultraviolet light with potential phototoxicity and low-tissue-penetrating depth as the irradiation source significantly hinders the further in vivo broad biomedical applications. Here, the very-recent development of novel exogenous physical irradiation of titania semiconductors for tumor-specific therapies based on their unique physiochemical properties, including near infrared (NIR)-triggered photothermal hyperthermia and photodynamic therapy, X-ray/Cerenkov radiation-activated deep-seated photodynamic therapy, ultrasound-triggered sonodynamic therapy, and the intriguing synergistic therapeutic paradigms by combined exogenous physical irradiations are in focus. Most of these promising therapeutic modalities are based on the semiconductor nature of titania nanoplatforms, together with their defect modulation for photothermal hyperthermia. The biocompatibility and biosafety of these titania semiconductors are also highlighted for guaranteeing their further clinical translation. Challenges and future developments of titania-based therapeutic nanoplatforms and the corresponding developed therapeutic modalities for potential clinical translation of tumor-specific therapy are also discussed and outlooked.