Ultrasound-driven self-decomposition porphyrins as metal-free CO precursors for gas and sonodynamic synergistic therapy

Carbon monoxide (CO) is an endogenous therapeutic gas with an anti-tumor effect. The precise delivery and controlled release of CO in tumor tissues play crucial roles in anti-cancer treatment. However, efficient in situ generation of CO from metal-free CO-releasing molecules (CORMs) remains a formidable challenge. Herein, we develop ultrasound (US)-driven self-decomposition porphyrin as organic and metal-free US-CORMs, which can spatiotemporally control the CO release (347 mmol CO/mol porphyrin) efficiently under physiologically harmless US conditions (1.0 MHz, 1.5 W/cm², 50% duty cycle, 50 min). Moreover, porphyrin as a sonosensitizer can also generate reactive oxygen species (ROS) under US treatment to achieve sonodynamic therapy (SDT). Advanced functions of such porphyrin-based CORMs in CO gas-sonodynamic synergistic treatment have been demonstrated by evaluating the in vitro and in vivo anti-tumor effects.