Platinum-Titania Schottky Junction as Nanosonosensitizer, Glucose Scavenger, and Tumor Microenvironment-Modulator for Promoted Cancer Treatment

To date, the construction of heterogeneous interfaces between sonosensitizers and other semiconductors or noble metals has aroused increasing attention, owing to an enhanced interface charge transfer, augmented spin-flip, and attenuated activation energy of oxygen. Here, a smart therapeutic nanoplatform is constructed by surface immobilization of glucose oxidase (GOx) onto a TiO2@Pt Schottky junction. The sonodynamic therapy (SDT) and starvation therapy (ST) mediated by TiO2@Pt/GOx (TPG) promote systemic tumor suppression upon hypoxia alleviation in tumor microenvironment. The band gap of TiO2@Pt is outstandingly decreased to 2.9 eV, in contrast to that of pristine TiO2. The energy structure optimization enables a more rapid generation of singlet oxygen (O-1(2)) and hydroxyl radicals (center dot OH) by TiO2@Pt under ultrasound irradiation, resulting from an enhanced separation of hole-electron pair for redox utilization. The tumorous reactive oxygen species (ROS) accumulation and GOx-mediated glucose depletion facilitate oxidative damage and energy exhaustion of cancer cells, both of which can be tremendously amplified by Pt-catalyzed oxygen self-supply. Importantly, the combinatorial therapy triggers intense immunogenetic cell death, which favors a follow-up suppression of distant tumor and metastasis by evoking antitumor immunity. Collectively, this proof-of-concept paradigm provides an insightful strategy for highly efficient SDT/ST, which possesses good clinical potential for tackling cancer.

Automated summary

The construction of a smart therapeutic nanoplatform consisting of TiO2@Pt/GOx (TPG) allows for efficient sonodynamic therapy (SDT) and starvation therapy (ST), which lead to systemic tumor suppression and hypoxia alleviation in the tumor microenvironment. The optimized energy structure of TPG enables rapid generation of singlet oxygen and hydroxyl radicals. The accumulation of reactive oxygen species and glucose depletion facilitated by TPG result in oxidative damage and energy exhaustion of cancer cells, amplified by Pt-catalyzed oxygen self-supply. The combinatorial therapy also triggers immunogenetic cell death and subsequent suppression of distant tumors and metastasis through antitumor immunity.