新型多功能有机纳米声敏剂对转移性骨肿瘤的治疗作用及其机制研究

骨是肿瘤最常见的转移部位之一，目前临床尚无普适的治疗策略对抗各类转移性骨肿瘤。作为一种新兴且实用型的治疗技术，声动力学治疗利用超声刺激声敏剂产生活性氧自由基，诱导癌细胞凋亡。前期研究发现，肿瘤处过量谷胱甘肽（GSH）会还原产生的活性氧自由基，降低疗效，进而导致肿瘤残留与复发。据此，本项目拟发展具备清除GSH能力的新型有机纳米声敏剂，并嫁接临床常用抗骨吸收药物唑来膦酸，实现“增强型”声动力学治疗并对抗转移性骨肿瘤。本研究拟制备的多功能有机纳米声敏剂，集骨/肿瘤双靶向、PET/荧光双模态影像于一体，兼备抗骨吸收/声动力学治疗协同对抗转移性骨肿瘤的双重功效。拟通过清除GSH、增强成骨细胞分化、抑制破骨细胞分化、杀死转移癌细胞来探讨声动力学治疗抑制转移性骨肿瘤的作用机制。本项目以研发新型多功能纳米声敏剂为目的，为临床对抗转移性骨肿瘤提供具有普遍适用的治疗策略。

The development of new technology in treating cancer to overcome the disadvantages of clinical chemo/radio-therapy is of great significance. In this project, a novel multifunctional organic nanosonosensitizer for enhanced sonodynamic therapy of bone metastases has been synthesized, which could dual-target bone metastases efficiently, diagnose them with PET/fluorescent imaging, and deplete GSH in tumor area to improve the production of reactive oxygen species under stimulation of ultrasound. Clinical anti-osteolysis drug of zoledronic acid (ZOL) is combined with sonodynamic therapy, which could inhibit tumor growth and relieve pain and bone resorption by inducing apoptosis in cancer cells and improving the bone microenvironment. This single organic nanoplatform combines ZOL and SDT to provide an exciting strategy for treating bone metastasis. The launching of this project is expected to promote the development of sonodynamic therapy and provide a universal strategy to treat different bone metastases.