A hypoxia-irrelevant Fe-doped multivalent manganese oxide sonosensitizer via a vacancy engineering strategy for enhanced sonodynamic therapy

Sonodynamic therapy (SDT), as a noninvasive treatment with preferable therapeutic depth, has attracted widespread attention. However, current sonosensitizers suffer from a low quantum yield of ultrasound (US)-triggered reactive oxygen species (ROS), and their efficacy is greatly compromised by hypoxia, a characteristic feature of most solid tumors. To address this issue, a hypoxia-irrelevant sonosensitizer, namely, Fe-doped multivalent manganese oxide nanoparticle (FDMN), was developed via an oxygen vacancy engineering strategy. The prepared FDMNs possessed sufficient oxygen vacancies (OVs) due to the doping of Fe3+ into the multivalent manganese oxide lattice, which allowed efficacious ROS generation by preventing the recombination of sono-triggered electron-hole pairs. Specifically, due to the OVs structures, oxygen molecules were adsorbed on the surface of FDMNs, bestowing nanosonosensitizers with a hypoxia-irrelevant singlet oxygen (O-1(2)) generation ability, which has not been shown before. Furthermore, FDMNs were capable of catalyzing endogenous O-2 into highly toxic O-1(2) without any exogenous stimulus to realize ROS overproduction, inherited from multivalent manganese oxides, and eliminating glutathione (GSH) to amplify the oxidative stress. All these synergistic effects result in a superior therapeutic outcome even in hypoxic microenvironment. Overall, this work illustrates that the vacancy engineering strategy is a favorable method to rationally construct a hypoxia-irrelevant sonosensitizer for highly efficient and safe SDT. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This study developed a hypoxia-irrelevant sonosensitizer through vacancy engineering strategy, which effectively prevented the recombination of ROS and generated hypoxia-irrelevant singlet oxygen. The results demonstrated that vacancy engineering is a favorable method for constructing highly efficient and safe sonodynamic therapy.