超顺磁一维柔性纳米组装型诊疗载体的构建与作用机制研究

项目名称： 超顺磁一维柔性纳米组装型诊疗载体的构建与作用机制研究

项目编号： No.81473160

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 熊非

作者单位： 东南大学

项目金额： 70万元

中文摘要： 肿瘤的早期诊断和靶向治疗是目前临床亟待解决的问题，靶向药物载体的尺寸、表面性质与靶向效应之间的关系已有较为清晰的理论，本项目针对目前球形载体靶向效率有限、一维材料仅限单一载药或单一影像功能、刚性一维材料的安全隐患等问题，从几何学、机械性能的新视角出发，构建一种以超顺磁性油酸包裹四氧化三铁纳晶为基本单元、两亲性聚合物双油酸-聚乙二醇-环状RGD衍生物为表面修饰材料、在磁场驱动和共溶剂交换共同作用下形成的一维柔性纳米组装型诊疗载体，通过研究磁场驱动下纳晶延磁力线方向一维组装生长的机制、以及形状、变形性与载体性质、生物效应之间的关系，揭示载体的作用机制和规律，构建一种体内安全可用的、兼具MRI功能、可多价靶向肿瘤新生血管的载阿霉素多功能超顺磁一维柔性纳米组装型诊疗载体，将载体的靶向能力提升到一个新水平，集早期诊断、实时监测和高效治疗于一体，为实现肿瘤靶向化疗及疗效追踪同步化的诊疗模式提供新思路。

中文关键词： 超顺磁性氧化铁纳米粒；一维组装体；柔性；肿瘤靶向；核磁共振成像

英文摘要： Early tumor detection and targeted tumor therapy have become an urgent problem in clinic. The theory of relationship between size, surface properties and targeting efficiency has been well established. To resolve the existing problem in targeted drug delivery system, such as the low targeting efficiency of spherical vehicles, single function of drug loading or imaging of one-dimensional materials, potential danger of rigid one-dimensional materials, we proposed a novel theranostic vehicle at the geometry and mechanical behavior level. Superparamagnetic one-dimensional flexible nano-assemblies (SOFNs) were constructed via extracorporeal magnetic driving and co-solvent exchange methods, which composed of oleic acid capped-Fe3O4 and dioleate-PEG-cRGDyK. After precise design and fabrication, the assembly and growth mechanism in the direction of magnetic induction line and relationship between shape, deformation ability and properties, bio-effects of SOFNs were researched. A safe, multivalent targeted SOFNs and assembly technology will be established for simultaneously chemotherapy and magnetic resonance imaging of tumor. Based on this research, tumor targeting of theranostic vehicle could be enhanced to a higher level, and a novel method for early diagnostics and high efficiency therapy will be established.

英文关键词： superparamagnetic iron oxide nanoparticles;one-dimensional assemblies;flexible;tumor targeting;MRI