诊疗一体化多级纳米超分子组装体的构建及提高肿瘤靶向输送的研究

项目名称： 诊疗一体化多级纳米超分子组装体的构建及提高肿瘤靶向输送的研究

项目编号： No.81471784

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： 李琳琳

作者单位： 北京纳米能源与系统研究所

项目金额： 73万元

中文摘要： 纳米药物为恶性肿瘤的治疗带来了希望，但肿瘤靶向性差，药物输送效率低仍是其致命的缺陷，临床应用中对病人总生存期的提高非常有限。旨在提高纳米药物的肿瘤靶向性、渗透性和疗效，本项目拟构建具有诊疗一体化功能的多级纳米超分子组装体，由具有影像和治疗功能的结构功能单元(磁性纳米颗粒，金荧光纳米团簇和抗肿瘤药物)组装而成。进入体内后，纳米超分子组装体整体尺寸有利于高效靶向到肿瘤组织，进行第一级输送。之后受到肿瘤微环境中过量表达的金属基质蛋白酶的刺激结构瓦解，释放小尺寸的结构功能单元，提高它们在肿瘤组织内的渗透、输送、影像与治疗，完成第二级输送。同时组装体瓦解过程中实现荧光发光的转变，可对肿瘤靶向治疗进行追踪监控。这种集磁共振、荧光影像、药物输送于一体的多级纳米超分子组装体通过肿瘤微环境的刺激实现尺寸和荧光性能的转变，可同时实现肿瘤高靶向性和高渗透性，为改善肿瘤治疗，实现癌症的个体化治疗开辟新的途径。

中文关键词： 诊疗一体化；纳米超分子组装体；肿瘤靶向和渗透；药物输送；肿瘤微环境

英文摘要： Nanomedicine has brought promising for cancer therapy, but they still have the limitation of low tumor targeting and drug delivery efficiency, which induce limited enhancement in overall survival in clinical application. For increasing tumor targeting, tissue penetration, and therapy efficacy of nanomedicine, this proposal aims to construct theranostic multistage supramolecular nanoassemblies from building blocks of magnetic nanoparticles, fluorescent gold nanoclusters, and therapeutic drugs for imaging and therapy. After entering body, the size of the intact supramolecular nanoassemblies is favorable for tumor targeting， acting as first-stage delivery. Then, with stimuli of overexpressed matrix metalloproteinases in tumor microenvironment, the supermocelular nanoassemblies would collapse and release the small-size building blocks, which is favorable for their tumor penetration, delivery, imaging and therapy, completing second-stage delivery. Meantime, the fluorescence would be changed in this course for monitoring the tumor targeted therapy. This kind of multistage supramolecular nanoassemblies with ability of magnetic resanance imaging, fluorescence imaging and drug delvery have tunable size and fluorescence with stimuli of tumor microenvironment, which can efficiently increase tumor targeting and penetration, silmutaneously. It paves a new avene for improving cancer therapy and realizing personalized therapy.

英文关键词： Theranostics;Supramolecular nanoassemblies;Tumor targeting and penetration;Drug delivery;Tumor microenvironment