Ultrasmall Oxygen-Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy

Abstract

Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue-penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen-deficient bimetallic oxide MnWO_X nanoparticles, for multimodal imaging-guided enhanced SDT against cancer. As-made MnWO_X nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWO_X -PEG nanoparticles exhibit highly efficient US-triggered production of ¹ O₂ and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen-deficient structure of MnWO_X serves as an electron trap site to prevent electron-hole recombination. The glutathione depletion capability of MnWO_X -PEG can also further favor SDT-triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWO_X -PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWO_X -PEG can be metabolized by the mouse body without any long-term toxicity. Herein, a new type of sono-sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Keywords: GSH depletion; MnWOX nanoparticles; bimetallic oxide; oxygen deficient; sonodynamic therapy.