项目名称： 超声/荧光双模态靶向纳米诊疗剂对胰腺癌HIFU治疗及化疗增效机制的基础研究

项目编号： No.81501473

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张坤

作者单位： 同济大学

项目金额： 18万元

中文摘要： HIFU因其无创治疗方式已成为胰腺癌治疗中一个新的研究热点，但目前HIFU增效剂均不具备一次给药多次增强HIFU消融以及监控消融过程的能力。前期工作中虽然我们利用无机氧化硅为载体构建出纳米诊疗剂实现了一次给药反复增强HIFU消融VX2兔肝肿瘤的治疗，但氧化硅载体存在降解性差、潜在的长期毒性等问题，同时工作未涉及靶向性以及与药物协同治疗研究。鉴于此，本课题以具有三相转变功能的固态薄荷醇取代传统的液态和气态氟碳化合物担载于生物相容性较好的聚合物中，克服传统的液态或气态化合物易于流动、泄露造成的结构坍塌以及与抗癌药物分子难混溶的缺陷，提高有机载体结构稳定性，然后通过结构化和功能化设计构建新型三相转变基靶向纳米诊疗剂，评价其在胰腺癌靶向、荧光/超声双模态诊断、三相转变介导HIFU消融增效以及与化疗协同治疗效果并研究其相应机制，为临床胰腺癌HIFU治疗提供新的治疗思路。

中文关键词： 高强度聚焦超声；超声/荧光双模式成像；靶向性；超声空化；协同治疗

英文摘要： HIFU treatment for pancreatic cancer has been a new research hotspot due to its invasive treatment character. The currently investigating HIFU enhancements agents failed in allowing multiple enhanced HIFU ablations under only once drug injection and monitoring ablation process. In previous work, we utilized inorganic silica as platform to construct a nanotheranostic agent that can achieve multiple enhanced HIFU ablations for VX2 tumors implanted in livers of rabbits under once drug injection in our previous work. However, the poor degradability and long-term toxicity of inorganic silica composition restrict the clinical translation, and simultaneously no targeting and no synergistic therapy constituting by loaded antitumor drug and HIFU ablation was implemented. Given this, in this project, solid L-menthol as inner core medium instead of conventional gas or liquid perfluorocarbon compounds was loaded in biocompatible polymers to overcome the drawbacks of gas or liquid compounds, e.g., facile fluidity and leakage resulted in structure collapse or deformation and high hydrophobic property made them immiscible with anti-tumor drugs, which is beneficial for improving the structure stability. Afterwards, marriage of structure and function designs will be integrated to construct a novel triphase transition-based targeted nanotheranostic agent, and concurrently performances and accordingly underlying principles of targeting, ultrasound/fluorescence bimodal imaging, triphase transition-controlled HIFU ablation and HIFU/chemotherapy synergistic treatment will be investigated, expectedly providing a new treatment avenue to clinical pancreatic cancer HIFU ablation.

英文关键词： high intensity focused ultrasound;ultrasound/fluorescence bimodal imagings ;targeting ;ultrasound cavitation;synergistic treatment