基于介孔磷酸钙的多功能响铃型结构纳米胶囊的通用制备方法及其在肝癌诊治中的应用研究

Nanomaterials have significant impact in cancer detection and theraphy due to its specific properties in nanoscale. With the emergence of multifuctional nanomaterials, the research of advanced nanodelivery system as early detection and diagnosis tools plays an important role in the novel method for cancer treatment and brings new hope to those suffering. The main process of this proposal is to design, sythesis and application. Based on the direction and stablization of PAA, we developed a novel and general approach to fabricate multifunctional mesoporous calcium phosphate based rattle type nanocapsules, which have the abilities of ultra-high drug loadings and pH responsed delivery system. Meanwhile, the nanoparticles can be changed to equip varials functions, such as upconversion imaging，MRI and photothermal therapy, which will provide the multi-model cancer image, simultaneous diagnosis and therapy. The aim of this proposal is to explore serials of calcium phosphate based rattle type nanocapsules, thereby allowing us to achieve controlled release of anticancer drugs in liver cancer cells. Our expertise in the rapidly developing techniques in the nanomaterials area is leading not only to new multifunctional materials but also to rapidly evolving and potentially useful theranostic tools to help humanity.

纳米材料由于其纳米尺度所固有的独特性质，在癌症的无创诊断与治疗方面起到了积极重要的作用。随着多功能纳米材料的出现为获得更加先进的药物输送系统和实现早期检测与诊断带来了新的希望，开辟了新的途径。本项目以"设计-合成-应用"为总体研究思路，借助聚丙烯酸（PAA）的导向与稳定作用，开发一种简单通用的方法制备基于介孔磷酸钙的多功能响铃型结构纳米胶囊，构筑出具有超高载药量及pH响应性的纳米药物输送系统，同时还可根据不同需要将上转换荧光成像、磁共振成像及光热治疗等技术用于其中，以实现对癌症的多模式成像、诊断与治疗。通过本项目的研究，可成功构建一系列基于磷酸钙的响铃型结构纳米胶囊，这对于开拓新型纳米材料，推进磷酸钙纳米材料在纳米医学领域的发展具有重要的理论意义和实际应用价值。

项目以“设计-合成-应用”为总体研究思路，开发简单易行的方法制备基于介孔磷酸钙的多功能纳米粒子，深入理解其形成机理。并拓展合成方，将其用于其它功能性纳米粒子的合成，构建对肿瘤多模式成像、化学、光热联合疗法和刺激响应释放药物于一体的新型纳米诊疗剂。项目实施三年来，集中开展了以下工作：.(1) 基于介孔磷酸钙多功能纳米粒子的合成及应用研究。我们开发了一种通用的方法合成基于介孔磷酸钙的多功能纳米生物探针，并将合成的材料进一步用于对肝癌的体内外荧光/热/CT成像诊断与药物输送及光热联合治疗。相关工作在Small, Chem. Commun., J. Mater. Chem. B等期刊发表。.(2) 基于PAA模版的多功能纳米粒子的合成及应用研究。我们以聚丙烯酸为模板制备一系列复杂结构多功能纳米粒子，并将其应用于体内外肝癌诊疗中。相关工作在Angew. Chem. Int. Ed., Small, Nanoscale, Chem. Commun.等期刊发表。.项目执行三年来，在Angew. Chem. Int. Ed., Small, Chem. Eur. J.等期刊上共发表学术论文10篇，其中2篇为封面文章；申请国家发明专利3项，较好的完成了既定任务。