Glutathione-depleting nanoplatelets for enhanced sonodynamic cancer therapy

Abstract

In combating cancer, ultrasound (US)-triggered sonodynamic therapy (SDT) manifests a wide range of promising applications as a noninvasive treatment modality, thus showing potential to overcome the shortcomings and disadvantages of conventional photodynamic therapy (PDT). Reactive oxygen species (ROS)-based therapy is practically destroyed by the high concentration of glutathione (GSH) inside tumors, and depleting GSH to improve the outcome of SDT is indeed a great challenge. Herein, we designed GSH-depleting nanoplatelets for enhanced sonodynamic cancer therapy. A platelet membrane coated nanosystem (PSCI) has been designed and tested comprising mesoporous silica nanoparticles (MSNs) which have been loaded with cinnamaldehyde (CA) as an oxidative stress amplifier. The inner layer comprises the sonosensitizer IR780 and the oxidative stress amplifier CA, whereas the platelet membranes (PM) were designed and utilized as an outer layer that can target tumors, thereby enhancing the effectiveness of SDT by attenuating the capability of tumor cells for scavenging ROS with GSH. SDT and cinnamaldehyde amplify oxidative stress by acting synergistically, leading to the preferential destruction of cancer cells in vitro and in vivo. It is hoped that next-generation tumor SDT treatments will find their way with the help of this strategy.