目前抗肿瘤治疗存在效率低、毒副作用大等问题，开发安全、高效的抗肿瘤药物和治疗手段具有重大意义。一氧化碳（CO）在抗肿瘤方面表现出独特的优势，但其体内运输难以调控，且缺乏有效的应用平台。本项目拟构建声敏CO纳米药物，实现超声调控下CO在肿瘤内的可控释放；同时充分发挥CO作为气体信号分子在敏化肿瘤细胞方面的优势，将CO气体治疗与声动力治疗有效结合，开展联合抗肿瘤治疗。具体地：(1)以声动力活性分子为构筑单元，制备得到尺寸均一、声动力活性优良的纳米MOF载体；(2)负载CO前体药物，并对纳米药物表面进行靶向修饰，提高纳米药物的靶向运输性能；(3)研究纳米药物结构与声动力活性的关系，获得超声作用下CO释放动力学方程，实现CO在肿瘤内的可控释放；(4)建立CO气体治疗与声动力治疗联合抗肿瘤的新模式，研究两种模式之间的协同作用机制。通过声敏CO纳米药物研究，有望为肿瘤的安全、高效治疗提供解决方案。

Current cancer therapy is challenged by low therapeutic efficacy and serious side effects. The developments of efficient antitumor drugs and modalities are highly important for cancer treatment. Nowadays, carbon monoxide (CO) has shown great potential in antitumor therapy. However, there are lack of efficient delivery systems and application platforms for CO. In this project we aim to design ultrasound-sensitive nanodrugs of CO. This kind of nanodrugs can remotely control CO release in tumors. More importantly, by virtue of the merits of CO as gasotransmitter, the nanodrugs can combine CO therapy and sonodynamic therapy together to increase the final antitumor efficacy with low side effects. This project will be carried out as follows. (1) MOF-based nanocarriers with homogeneous size distribution and excellent sonodynamic activity will be designed and fabricated. (2) CO prodrugs will be loaded into the nanocarriers. Meanwhile, targeting molecules will be functionalized on the surface of the nanocarriers to realize tumor targeting delivery. (3) The relationship between the structures and sonodynamic activity of the nanodrugs will be investigated. The kinetic equations of CO release under ultrasound irradiation will be studied, and the methods of regulating CO release under ultrasound will be also summarized. (4) This project will innovatively combine CO-based gas therapy with sonodynamic therapy. Understanding the synergy between these two therapeutic modalities will pave the way for the clinical translation of the nanodrugs. Therefore, we believe this kind of nanodrugs will provide a new strategy for safe and efficient tumor therapy.