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 oxygenindependent, 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-NMe2displays 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-NMe2has made it a powerful tool for the efficient treatment of hypoxic tumor.