光热诱导相变型超声响应性载药纳米囊用于肿瘤协同治疗的研究

It is a major challenge to achieve highly efficient antitumor therapy in cancer treatment. Drug nanocarriers with synergistic antitumor capabilities are considered as a promising strategy for cancer therapeutic efficacy improvement. In this application, we propose to develop novel ultrasound responsive drug-loaded nanocarriers based on Doxorubicin and Cypate co-encapsulated liquid perfluorocarbon (PFC) nanocapsules for synergistic chemo-photothermal antitumor therapy. Photothermal effect of Cypate upon near infrared laser irradiation could not only directly induce tumor cell necrosis for efficient photothermal therapy (PTT), but also result in liquid-gas phase transition of PFC to form microbubbles. The interaction between ultrasound irradiation and microbubbles will trigger responsive release of Doxorubicin, and enhance cellular delivery via sonoporation to significantly improve chemotherapy. Therefore, highly efficient antitumor efficacy could be achieved through synergistic chemo-photothermal therapy facilitated by multiple functionalities of photothermal effect. The application will elucidate the key role of photothermal effect induced liquid PFC phase transition in ultrasound responsive drug delivery, and the mechanism of synergistic effect between PTT and chemotherapy. This work has great potential to provide theoretical and practical basis for the development of efficient antitumor therapeutic strategy by exploring novel stimuli responsive drug nanocarriers, and will be highly valuable in anticancer research and application.

肿瘤的高效治疗是癌症治疗领域面临的重大挑战，构建新型纳米药物载体实现肿瘤协同治疗，是提高癌症治疗效果的有效手段。本项目拟采用相变型液态氟碳纳米载体，同时携载光吸收剂碳菁染料和化疗药物阿霉素，构建新型超声响应性载药纳米囊，进行肿瘤协同治疗研究。利用近红外光辐照下碳菁染料的光热效应，不仅能够引起肿瘤细胞急性坏死，直接进行光热治疗，还可诱导液态氟碳相变形成微泡，实现超声响应性药物释放，并通过声孔效应将药物快速高效的输送进入细胞，显著增强化疗效果。利用光热效应的多重作用，有望通过光热治疗与化疗的协同增效，实现肿瘤高效治疗。本项目通过阐明光热效应诱导的液态氟碳相变在超声响应性药物输送中的关键作用，明确光热治疗与化疗的协同作用机制，有望探索新型响应性纳米药物载体，为开发高效的肿瘤治疗方法提供有益的理论和实践依据，具有较大的理论研究意义及潜在应用价值。

肿瘤的高效治疗是癌症治疗领域面临的重大挑战。本项目发展了同时携载化疗药物顺铂前药和碳菁染料Cypate的多功能载药聚合物胶束，通过Cypate在近红外光照下所产生的高热效应，不仅可产生光热损伤，还可有效抑制耐药肿瘤细胞中多药耐药蛋白（MRP1）的表达量，显著提升顺铂药物的化疗效果，实现高效的肿瘤光热/化疗协同治疗，并阐明了光热治疗与化疗的协同作用机制。同时采用硫化铜白蛋白纳米粒和氧化钆白蛋白纳米粒作为油水界面稳定剂，包裹相变型液态氟碳化合物，构建了相变型超声响应性纳米囊，通过诱导液气相变和声孔效应，实现纳米粒在肿瘤细胞的直接、高效递送，用于肿瘤高效治疗。在本项目的资助下，项目负责人作为通讯作者在Adv Mater、ACS Nano、Small等高水平国际期刊发表SCI论文5篇，其中影响因子大于10的论文2篇，获得授权中国发明专利2项。