Chemodynamic therapy agent optimized mesoporous TiO nanoparticles for Glutathione-Enhanced and Hypoxia-Tolerant synergistic Chemo-Sonodynamic therapy.

Sonodynamic therapy (SDT) can generate reactive oxygen species to kill cancer cells by activating sonosensitizers under ultrasound (US) irradiation. Nevertheless, its application is greatly limited by low quantum yield of sonosensitizers, high levels of endogenous glutathione (GSH) and tumor hypoxia. Herein, a GSH-activated sonosensitizers with synergistic therapy effect (chemodynamic therapy (CDT) and SDT) are developed by depositing Fe(III)-artemisinin infinite coordination polymers (Fe(III)-ART CPs) in pores of mesoporous TiO nanoparticles (NPs). The formed Fe(III)-ART-TiO NPs have high sono-induced electron-hole separation efficiency because the deposited Fe(III)-ART CPs can provide isolated intermediate bands to capture sono-induced electrons in TiO NPs. Meanwhile, Fe in Fe(III)-ART-TiO NPs are reduced to Fe by GSH with oxygen-deficient sites generated to further capture sono-induced electrons in TiO NPs. Based on this, the reaction efficiency between water molecules and sono-induced holes is high enough to generate numerous hydroxyl radicals (•OH) without oxygen participated for overcoming tumor hypoxia. Additionally, through consuming GSH, the generated Fe can catalyze ART to produce C-centered free radicals for CDT. Owing to these characteristics, Fe(III)-ART-TiO NPs show significant tumor suppression ability and good biocompatibility in vivo. The strategy of using CDT agent to modify sonosensitizers offers new options to improve SDT effect without introducing harmful substances.