肿瘤微波热疗增敏的响应监测原理研究

To obtain a kind of technique based on the novel multifunctional nanocomposites that owns tumor microwave thermotherapy and multi-mode targeting-imaging-therapy properties simultaneously, the double-shell mesoporous and hollow ZrO2 particles are designed as the key materials to encapsulate the microwave hyperthermia and multi-functional imaging units into the shell, and to couple target molecules and microwave switches onto the surface of the shell. The multi-functional materials enrich in the tumor site through the active targeting and EPR effect. The confinement effect of the double-shell mesoporous and hollow ZrO2 particles make the GTD have high microwave heat transfer efficiency to heat up quickly to kill tumor cells under microwave irradiation. Moreover, under the action of microwave field, the temperature-sensitive switches are opened, the ratio of fluorescence probe in ZrO2 sense the concentration of hydrogen peroxide in the tumor microenvironment. Based on the CT imaging enhancement properties of ZrO2, the MRI imaging properties of GTD and the positioning function the ratio of fluorescence probe that loaded in the ZrO2, we can real-time monitor the therapeutic outcomes visually and adjust the microwave thermal dose promptly, which can avoid the tumor recrudescence and the thermal injury to normal tissues. The novel multifunctional nanocomposites integrate various biomaterials and tumor theranostic techniques, which is a new innovation in tumor comprehensive therapy and may result in the development of multidisciplinary technique of tumor comprehensive therapy.

利用纳米材料与电磁波相互作用机制发展的肿瘤治疗与影像技术是当前纳米生物医用热点研究领域。本项目以具有CT影像增强功能的双壳中空介孔二氧化锆为载体，负载微波热疗增敏与多种影像功能单元，表面偶联靶向分子与微波开关，发展多模式实时监测肿瘤微波热疗响应的纳米复合功能材料与理论。通过主动靶向与EPR效应在肿瘤部位富集；微波辐照下二氧化锆中空球的限域作用使GTD具有高效的微波热转换效率，迅速升温杀死肿瘤细胞；微波场作用下打开敏感开关，使二氧化锆内部的比率荧光探针感知肿瘤微环境中产生过氧化氢活性成分的浓度，利用二氧化锆自身的CT影像增强功能与中空球装载GTD的MRI增强功能，CT、MR影像与荧光比率探针共定位，实时监测肿瘤微波热疗响应，评价治疗效果。本项目整合集成了多种新型生物信息获取、处理与融合基本理论，是肿瘤的跨界综合信息技术的一次实践，引导创新型、多学科交叉的肿瘤生物信息学的发展。

利用纳米材料与电磁波相互作用机制发展的肿瘤治疗与影像技术是当前纳米生物医用热点研究领域。本项目旨在解决微波消融技术在临床肝癌治疗中所遇到的热量投递有效性与安全性不可控等关键科学问题，遵循材料按需制备的原则，设计新型微波响应纳米复合功能材料与技术。以具有CT影像增强功能的双壳中空介孔二氧化锆为载体，研制集靶向技术、微波热疗增敏、CT影像、MR影像与荧光多模影像的“All-in-One”的纳米复合结构。研究主动靶向与EPR效应增加纳米药物载体在肿瘤部位富集。微波辐照下介孔中空二氧化锆的限域作用使其具有高效的微波热转换效率，迅速升温杀死肿瘤细胞。微波场作用下打开敏感开关，控制释放化疗药物等治疗单元。探索高灵敏度、高分辨率、高准确性地监测肝癌微波靶向增敏热疗响应与治疗效果，为微波热疗增敏技术提供实验依据和奠定理论基础。在探索微纳结构材料在选择性微波热疗应用的新方向同时，深入研究微波非热电磁生物效应理论机制，开拓肿瘤微波治疗新领域。本项目整合集成了多种新型生物信息获取、处理与融合基本理论，是肿瘤的跨界综合信息技术的一次实践，引导创新型、多学科交叉的肿瘤生物信息学的发展。.在本项目的资助下共发表学术论文27篇，取得授权发明专利5项；培养多名研究生，四名研究生获得国家奖学金，两名研究生获得中科院院长奖；两名研究人员得到职称晋升。