LAUSR

Ferroptosis has recently attracted much attention as an anti-tumor therapy. Evidence suggests that ferroptosis can induce oxidative stress and accumulation of lethal lipid peroxides in cancer cells, leading to cell damage. However, unsuitable pH, H2 O2 levels, and high glutathione (GSH) expression in the tumor microenvironment hinder the development of ferroptosis-mediated therapy. In this study, an L-arginine (L-arg)-modified CoWO4 /FeWO4 (CFW) S-scheme heterojunction was strategically designed and constructed for ultrasound (US)-triggered sonodynamic- and gas therapy-induced ferroptosis. CFW not only has excellent Fenton-catalytic activity, outstanding GSH consumption capacity, and excellent ability to overcome tumor hypoxia, but its S-scheme heterostructure can also avoid the rapid combination of electron (e) and hole (h+ ) pairs, thereby enhancing the sonodynamic effects. As a precursor of nitric oxide (NO), L-arg was modified on the surface of CFW (CFW@L-arg) to achieve controlled NO release under US irradiation, thereby enhancing ferroptosis. In addition, poly(allylamine hydrochloride) (PAH) was further modified on the surface of CFW@L-arg to stabilize L-arginine and achieve controllable NO release. Both in vitro and in vivo results demonstrated that such a multifunctional therapeutic nanoplatform can achieve high therapeutic efficacy through sonodynamic and gas therapy-enhanced ferroptosis. Our designed oncotherapy nanoplatform provides new inspiration for ferroptosis-mediated therapy. This article is protected by copyright. All rights reserved.