新型双控纳米复合药物载体的构筑及其可控释放研究

Chemotherapy is an absolutely necessarily therapeutic method of malignant tumor. However, most commonly used anticancer drugs are not specifically toxic to tumor cells and are toxic to all tissues they contact so they create undesirable side effects as a result of their interactions with normal tissues. These toxic side effects hinder their development and applications. In this project, according to our previous study of biomaterials, nanosized hydroxyapatite or doping hydroxyapatite with good dissolubility and drug loading property will be produced using double template technology. Furthermore, in order to enhance the concentration for enhanced diffusion to the diseased cells and minimize the side effeets of drugs, some novel dual-directed drug delivery systems will be prepared by heteroepitaxial growth using superparamagnetic material, targeting ligand and hydroxyapatite nanoparticle as fundamental units. It will be spent a lot of care in finding out the process along which the anticancer drug can be guided to a desired site and selectively attack tumor cells with the aid of dual-directed drug delivery nanocomposites. The inherent interrelation between the release behavior of dual-directed drug delivery nanocomposite and doped ions, the content of the ions, and the external magnetic field will be studied in detail. The mechanism of the formation of drug delivery nanocomposites will be also discussed.To get the optimum dual-directed drug delivery systems, many factors such as preparation process and effect of targeting will be investigated. This study will provide a simple and feasible way for preparation of other anticancer drugs, extending the application domain of biomaterials.

化疗是癌症治疗中不可或缺的方法，但目前而言，化疗药物缺乏靶向性，毒副作用强，严重地制约了其发展与应用。本项目拟在前期生物材料研究的基础上，以新型双模板技术和异质外延生长技术为基础，设计合成具有良好载药与缓释性能的纳米羟基磷灰石（HA）及掺杂体；再以其为主要构建基元，超顺磁材料为磁导向物质，特异性靶向配体为肿瘤细胞识别分子，构筑新型双控给药体系，精确给药，控制释放，高效杀伤肿瘤细胞。分析双靶向技术（定位病灶的磁靶向与特异性识别肿瘤细胞的细胞靶向巧妙结合）实现药物仅在病灶富集及对肿瘤细胞识别攻击的作用规律，研究掺杂离子种类、掺杂量及外加磁场强度、施加方式与载药粒子的释放行为的内在联系，完成药物可控释放，探讨给药体系的构筑机理及其杀伤肿瘤细胞的作用机理。从给药体系的构筑过程及给药性能的影响因素等诸多方面进行系统研究，为制备新型高效抗肿瘤药物开辟新的途径，拓展生物材料的应用领域。

化疗是癌症治疗中不可或缺的重要组成部分，但目前而言，大多化疗药物毒副作用强、缺乏靶向性，严重影响了其疗效，成为中晚期恶性肿瘤治疗的瓶颈。本项目构建了由离子液体、高分子微球、生物大分子聚合物等组成的新型双模板调控体系，实现了不同微结构与载药性能的HA载体基质的制备，得到了空心球、纳米晶粒聚集球、花状结构等具有高吸附性能的HA纳米材料。再以其为主要构建基元，超顺磁材料（Fe3O4等）为磁导向物质，特异性靶向配体为肿瘤细胞识别分子，构筑了新型核壳结构等双控给药体系，精确给药，控制释放，对肿瘤细胞具有高效的杀伤力。并依据本研究方向的前沿动态，在此基础上，引入具有强吸附性能的MOFs材料作为载药基质，拓展了新型的高效载药材料；在传统的药物杀伤癌细胞的基础上，结合光线态氧抑制癌细胞，构建新型的PEGDA凝胶靶向给药体系、灭杀癌细胞。分析了不同靶向技术实现药物仅在病灶富集及对肿瘤细胞识别攻击的作用规律，研究复合药物载体的结构、磁性物质种类及外加磁场与载药粒子的释放行为的内在联系。初步探讨了给药体系的构筑机理及其杀伤肿瘤细胞的作用机理。从给药体系的构筑过程及给药性能的影响因素等诸多方面进行了系统研究，为制备新型高效抗肿瘤药物开辟新的途径，拓展生物材料的应用领域。