基于纳米核壳结构的多功能药物靶向控释系统的合成及抗肿瘤性能研究

项目名称： 基于纳米核壳结构的多功能药物靶向控释系统的合成及抗肿瘤性能研究

项目编号： No.21471041

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 曲凤玉

作者单位： 哈尔滨师范大学

项目金额： 92万元

中文摘要： 本项目以材料科学和医药学理论为依据，以抗癌性能为导向，致力于多功能药物靶向控释系统的研究。采用介孔二氧化硅纳米核壳结构材料作为药物载体，以设计合成的具有酶响应和pH敏感性的修饰剂，对载体材料进行多功能修饰与组装，实现基于癌细胞区域富集的还原性谷胱甘肽与微酸性环境的靶向药物控释，在磁热疗的协同作用下提高对癌细胞的毒性；同时，合成以金纳米棒为核，聚吡咯为壳的双重光热疗抗癌复合体系。结合细胞实验，研究材料的生物相容性，以及药物、磁热和光热多重性能协同作用对癌细胞毒性的增强作用。详尽地表征合成材料的结构，建立材料结构、药物控释机制、磁/光热疗与抗癌性能之间的关系；总结多功能药物控释体系的合成，功能化修饰与药物组装的技术；评价该体系的抗癌性能，为多重性能（药物靶向释放、磁热和光热）协同治疗癌症及高效安全的抗肿瘤药物的临床应用提供可靠的研究数据。

中文关键词： 核壳结构；靶向控释；光热疗；抗肿瘤

英文摘要： Oriented by the anti-cancer properties, the multifunctional-targeted control drug release system is dedicated in light of the material and medical theories. Mesoporous silica core-shell nanomaterials, uesed as the carriers, are multifunctionally modified and assembled by the designed and synthesized modifiers with enzyme response and pH sensitivity. The drug delivery systems are employed to target the drug release for the glutathione (GSH) enriching in the cancer and less-acidic environment, increasing the cancer cytotoxicity under the magnetic hyperthermia synergism. Meanwhile, polypyrrole (PPy) is used to coat outside of gold nanorod, obtaining the Au@PPy nanocomposites possessing dual photothermal anti-tumor system. Cell experiments are carried out to evaluate the biocompatibility and the cytotoxicity by the multi-therapy technology (e.g. anti-tumor drug, magnetic hyperthermia and photothermal). The obtained materials are systematically characterized, and the relationship is established between material structures, drug release mechanism, magnetic hyperthermia/photothermal, and anti-cancer properties. The strategies of synthesis, modification, and drug assembly are summarized for the multifunctionally controlled drug delivery systems, and the anti-cancer properties of the systems are evaluated. The project enble to offer reliable data not only for the synergistic antitumoral effects (anti-tumor drug, magnetic hyperthermia and photothermal), but for the application of the efficient and safe clinic al antitumor drugs.

英文关键词： core-shell structure;targeted drug release;photo-thermal therapy;anti-tumour