叶酸受体靶向的超顺磁/荧光/VEGF siRNA多功能硅纳米载体的抗肿瘤作用及其成像规律研究

项目名称： 叶酸受体靶向的超顺磁/荧光/VEGF siRNA多功能硅纳米载体的抗肿瘤作用及其成像规律研究

项目编号： No.81201192

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 杨红

作者单位： 电子科技大学

项目金额： 23万元

中文摘要： 靶向可控的药物/基因纳米载体被称为"梦的制剂"。抗血管生成疗法以其效果稳定、不易产生耐药性、毒副作用小等特点，成为肿瘤治疗研究的热点之一。本项目以构建叶酸受体靶向的超顺磁/荧光/VEGF siRNA多功能硅纳米载体选择性识别肿瘤细胞表面特定高表达的分子标记物叶酸受体（folate receptor, FR），提高对肿瘤细胞(或组织)的选择性识别和在靶细胞上可控聚集为出发点，深入而系统地研究此纳米载体系统的合成条件、特性表征、输送效果、细胞内分布规律、纳米载体代谢规律（动力学）、目标蛋白VEGF表达抑制效果及肿瘤血管新生抑制情况，以此来评价纳米基因载体的靶向治疗效果。然后利用干扰细胞内吞途径的特异性抑制剂，分析和探讨此多功能硅纳米基因输送载体被肿瘤细胞内吞的分子机制与转运机理，同时建立动物模型，重点分析在体条件下的抗肿瘤效果和荧光成像规律，为其最终的临床应用提供实验数据和参考信息。

中文关键词： 复合纳米载体；叶酸受体靶向；VEGF siRNA；基因/药物共输送；诊疗一体化

英文摘要： Targeted and controlled drug/gene delivery systems are called "mystic pharmaceutics". Angiogenesis is the formation of new blood vessels from preexisting microvessels. In particular, tumor growth and metastasis were found to be dependent on angiogenesis. Thus, anti-angiogenic therapy has become an important route for cancer treatment. This strategy for anti-cancer therapy has many excellent traits, for instance, good effect, low toxicity, and almost no drug resistance. Many literatures reported that anti-angiogenesis by inhibition of VEGF has been considered as a promising approach to suppress growth and metastasis of malignant tumors. However, the use of siRNA in clinical applications is still questioned because of its inherent instability in biological fluids along with poor or non-specific cellular uptake. To address these problems, non-viral delivery systems based on nanoparticles have been introduced for siRNA. In the present research proposal, a new and multifunctional delivery system for VEGF siRNAs will be developed. The multifunctional carriers are core-shell structure (Fe3O4@SiO2), and fluorescent dye molecules (FITC) were doped into the silica shells. Then surface modification will be further carried out for conjugating folate and VEGF siRNA to form a novel type of multifunctional nanoparticle complex

英文关键词： Nanocomplexes；Folate receptor targeting；VEGF siRNA；Gene/drug co-delivery；Theranostics