CoOx‐Caged Metal‐Organic Frameworks for Sonocatalyzing CO2 to Co for Ultrasound‐Assisted Chemodynamic‐Gas Cancer Therapy

Abstract Carbon monoxide (CO) as an endogenous gaseous signaling molecule, is widely studied for its ability to inhibit cancer cell proliferation as gas therapy. However, the therapeutic efficiency of CO gas therapy is far from ideal due to the low availability of CO supply. Here, inspired by the band structure and Fenton‐related elements, MIL‐101(Cr)@CoOx nanoparticles are introduced for the first time to achieve ultrasound‐mediated synergistic therapy by combining CO gas therapy and chemodynamic therapy together effectively. MIL‐101(Cr)@CoOx can present substantial CO 2 adsorption capacity for the BDC 2− linkers and Co center, and enable to transformation of endogenous CO 2 to CO efficiently under ultrasound irradiation due to the appropriate band structure and conduction band position. With the Co‐engaged Fenton‐like reaction, MIL‐101(Cr)@CoOx triggered the reactions to catalyze the over‐expressed intracellular H 2 O 2 into cytotoxic hydroxyl radicals (·OH). The potential therapeutic outcome of chemodynamic therapy can be amplified by the ultrasonic cavitation‐induced conversion between Co 3+ and Co 2+ in vitro is demonstrated. The proliferation, ATP, and mitochondria functions of 4T1 mouse breast cancer cells are severely compromised by CO‐promoted ROS generation and the sono‐Fenton effect. Further, in vivo studies confirm that MIL‐101(Cr)@CoOx combined with ultrasound irradiation exhibits superior tumor suppression, and achieves the ultrasound‐mediated chemodynamic‐gas cancer therapy with higher precisions for personalized treatments. This new system offers a distinct concept for constructing smart ultrasound‐stimulus systems to realize synergetic cancer therapy.