多功能纳米相变液滴多策略增强声动力效应的生物物理机制

To overcome the low tumor specificity of sonosensitizer, reduced efficiency and unclear treatment mechanism of sonodynamic therapy (SDT), this project is planned to synthetize a multifunctional phase-change nanodroplet for enhancing sonodynamic effect with a multi-strategic approach and further clarify its potential biophysical mechanisms. The main contents go as follow: 1) The multifunctional nanodroplet was designed and synthetized for targeted delivery and controlled release of sonosensitizer, enhancing the bioeffects of acoustic cavitation and manipulating tumor microenvironment, then its structure and properties were investigated; 2) Theoretical models and key experimental techniques, such as high-speed microscopic imaging and passive cavitation detection, were established to elucidate the transient physical processes during the acoustic cavitation of nanodroplet, and the quantitative relationships between acoustic cavitation and the key physical/chemical processes in SDT (i.e., the release of sonosensitizer, oxygen supply, glutathione consumption and generation of reactive oxygen) were further revealed; 3) The quantitative evaluation of enhanced SDT was performed with in vitro and in vivo experiments and its biophysical mechanism was clarified. In this project, the biophysical mechanism of enhanced sonodynamic effect induced by a multi-strategic approach with multifunctional phase-change nanodroplets was clarified theoretically and experimentally, providing an important theoretical foundation for developing a precise, efficient and safe SDT scheme.

针对目前肿瘤声动力疗法（SDT）中声敏剂靶向性差、肿瘤微环境降低疗效和治疗机制不清等突出问题，本项目提出构建一种多功能纳米相变液滴以多策略方式增效SDT并阐明潜在的生物物理机制。具体包括：1）设计制备可同时实现靶向递送与可控释放声敏剂、增强空化生物学效应和操纵肿瘤微环境的多功能纳米相变液滴并完成结构与性能的定征分析；2）建立理论模型和高速显微成像、被动空化检测等关键实验技术，阐明纳米液滴声空化瞬态物理过程，并揭示声空化与SDT中声敏剂释放、氧气供应、谷胱甘肽消耗和活性氧生成等关键物理/化学过程之间的定量关系；3）体外和体内实验实现纳米液滴增效SDT的定量化评价，并阐释其生物物理机制。本项目在构建多功能纳米相变液滴的基础上，从理论和实验两方面，阐明了纳米相变液滴多策略增强声动力效应的生物物理机制，为发展一种精准、高效和安全的肿瘤SDT技术奠定重要理论基础。

声动力疗法作为一种无损靶向的肿瘤治疗新方法，近年来国内外相关研究取得了瞩目的进展，但目前仍存在声敏剂靶向性差、肿瘤微环境降低疗效和治疗机制不清等突出问题，进而限制了其临床转化应用。对此，本项目提出构建一种多功能纳米相变液滴以多策略方式增强声动力效应并阐明潜在的生物物理机制。项目首先完成了多功能纳米液滴的设计制备与定征分析，该纳米液滴可实现声敏剂肿瘤靶向递送与可控释放、增强声空化力生物学效应和操纵改善肿瘤微环境；进而，建立了空化物理过程理论模型和高速显微成像、被动空化检测等关键实验技术，完成了纳米液滴声空化成核和动力学物理过程以及空化微泡非线性振动、声辐射信号特征、惯性空化阈值和空化力学效应等典型特性分析；最后，实现了纳米液滴多策略增效肿瘤声动力效应的定量评价，并且阐释了内在的生物物理机制。本项目按计划完成了主要研究目标与内容，相关研究成果可为发展一种精准、高效和安全的肿瘤声动力治疗技术奠定重要理论基础。项目执行期间，部分研究成果已以项目负责人第一作者或通讯作者身份在国内/国际知名期刊发表了项目相关论文7篇；培养硕士研究生4名；支持本科生科研训练计划2项，创新项目1项；积极开展了国内外学术交流活动，参加领域内高水平国内/国际会议。

内容获取失败，请点击重试