Sono-ReCORMs for synergetic sonodynamic-gas therapy of hypoxic tumor

Carbon monoxide (CO) gas therapy, a novel anti-tumor technique based on the cytotoxicity from the CO released in situ, has become one of the hot topics in cancer treatment. Since the technique is oxygen-independent, it displays promising therapeutic effect for hypoxic tumor where traditional photodynamic therapy shows limited efficacy and insufficient penetration depth. To fully address these limitations of PDT, we propose a synergetic sonodynamic-CO gas releasing strategy for the therapy of hypoxic tumor. In this work, two rhenium(I) tricarbonyl complexes with different substituted ligands are investigated for US-triggered ROS generation and CO release. Our results indicated that the electron-donating NMe2-substituted complex (Re-NMe2) exhibits stronger luminescence intensity and generates more singlet oxygen (1O2) than the electron-withdrawing NO2-substituted complex (Re-NO2). In addition, Re-NMe2 displays release of CO triggered by US, thus showing high sono-cytotoxicity to tumor cells in-vitro and in-vivo. The strong ROS-generating capability combined with rapid CO-releasing feature from Re-NMe2 has made it a powerful tool for the efficient treatment of hypoxic tumor.