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-MnO2@CCM (AMBC) was prepared by loading O2 generator MnO2 nanoparticles (NPs) and alkyl radical generator 2,2-azobis [2-(2-imidazoline-2-yl) propane] dihydrochloride (AIPH) into porous SiO2 grown with TiO2 NPs (MSTN), followed by coating with OC cell membrane (CCM). The MnO2 not only can be reduced by GSH to Mn2+ for T1-weighted magnetic resonance (MR) imaging but also catalyzes the decomposition of endogenous H2O2, providing sufficient O2 for the production of reactive oxygen species (ROS) induced by TiO2. Under the action of US, AIPH decomposes to produce alkyl radicals and N2, which further enhances the acoustic cavitation effect of TiO2 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.