Ultrasound and glutathione dual-responsive biomimetic nanoplatform for ultrasound/magnetic resonance imaging and sonodynamic therapy of ovarian cancer.

Sonodynamic therapy (SDT) has emerged as a promising treatment method for unresectable ovarian cancer (OC) due to its deeper permeability and absence of phototoxicity. However, the low targeting efficiency of sonosensitizers and the hypoxic tumor environment limit the efficacy of SDT, posing significant challenges to tumor treatment. Herein, an ultrasound (US) and glutathione (GSH) dual-responsive SDT nanoplatform, AIPH-MSTN@BSA-MnO@CCM (AMBC) was prepared by loading O generator MnO nanoparticles (NPs) and alkyl radical generator 2,2-azobis [2-(2-imidazoline-2-yl) propane] dihydrochloride (AIPH) into porous SiO grown with TiO NPs (MSTN), followed by coating with OC cell membrane (CCM). The MnO not only can be reduced by GSH to Mn for T-weighted magnetic resonance (MR) imaging but also catalyzes the decomposition of endogenous HO, providing sufficient O for the production of reactive oxygen species (ROS) induced by TiO. Under the action of US, AIPH decomposes to produce alkyl radicals and N, which further enhances the acoustic cavitation effect of TiO and promotes the production of ROS and enhances US imaging. In addition, CCM, with its homologous targeting and immune escape properties, enables AMBC to be targeted and delivered to tumor cells. Together, this work constructs a novel sonodynamic nanoplatform with homologous targeting and superior hypoxia-overcoming ability for efficient SDT of OC, guided by US/MR dual-mode imaging.