MOF-derived Nanoparticles with Enhanced Acoustical Performance for Efficient Mechano-Sonodynamic Therapy.

Ultrasound generates toxic reactive oxygen species (ROS) by acting on sonosensitizers for cancer treatment, and the mechanical damage induced by cavitation effects under ultrasound is equally significant. Therefore, designing a novel sonosensitizer that simultaneously possesses efficient ROS generation and enhanced mechanical effects is promising. In this study, we construct carbon-doped zinc oxide nanoparticles (C-ZnO) for mechano-sonodynamic cancer therapy. The presence of carbon doping optimizes the electronic structure, thereby enhancing the ROS generation triggered by ultrasound, efficiently inducing tumor cell death. On the other hand, the high specific surface area and porous structure brought about by carbon doping enable C-ZnO to enhance the mechanical stress induced by cavitation bubbles under ultrasound irradiation, causing severe mechanical damage to tumor cells. Under the dual effects of sonodynamic therapy and mechanical therapy mediated by C-ZnO, excellent anti-tumor efficacy was demonstrated both in vitro and in vivo, along with a high level of biological safety. This is the first instance of utilizing an inorganic nanomaterial to achieve simultaneous enhancement of ROS production and ultrasound-induced mechanical effects for cancer therapy. This holds significant importance for the future development of novel sonosensitizers and advancing the applications of ultrasound in cancer treatment. This article is protected by copyright. All rights reserved.