Ultrasmall Oxygen‐Deficient Bimetallic Oxide MnWO<i>_X</i> Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy

TLDR

Sonodynamic therapy triggered by ultrasound has gained attention for its ability to overcome the limited tissue penetration and phototoxicity of photodynamic therapy. The study designs ultrasmall oxygen‑deficient bimetallic oxide MnWOX nanoparticles as a multimodal imaging‑guided sonosensitizer to enhance cancer SDT. These MnWOX‑PEG nanoparticles generate high levels of singlet oxygen and hydroxyl radicals upon ultrasound, owing to oxygen‑deficient sites that trap electrons and suppress electron–hole recombination. The MnWOX‑PEG particles exhibit excellent biocompatibility, efficient tumor accumulation, potent ROS production and glutathione depletion, leading to effective tumor ablation under ultrasound with rapid clearance and no long‑term toxicity.

Abstract

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 O 2 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.