智能化双靶向肿瘤光学/核素/MRI多模态分子探针的合成及其性能研究

项目名称： 智能化双靶向肿瘤光学/核素/MRI多模态分子探针的合成及其性能研究

项目编号： No.81471727

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： 刘鉴峰

作者单位： 中国医学科学院

项目金额： 72万元

中文摘要： 肿瘤的早期准确诊断是目前提高肿瘤治愈率最为有效的手段之一，而多模态分子影像是肿瘤早期准确诊断的有效工具。多模态纳米分子探针能够很好的解决多模态影像中不同探针之间比例不同的问题，但存在着如何更好提高肿瘤靶向性及增强肿瘤内渗透性的问题。本项目拟将具有大量表面活性基团的聚酰胺-胺型（PAMAM）树枝状高分子材料连接至二氧化硅包覆超顺磁四氧化三铁的纳米粒上，制备具有超顺磁性的PAMAM-Fe3O4@SiO2纳米材料，以前期课题组自主筛选获得的肿瘤靶向多肽为靶向剂，进一步连接肿瘤穿透肽iRGD及能够进行电荷转变的聚β氨酯来制备对肿瘤微环境具有智能响应性的双靶向及高肿瘤渗透性的纳米载体。通过在纳米载体上标记荧光分子Cy7和碘[131I]来合成可以对肿瘤同时进行光学/放射性核素/MRI成像的肿瘤多模态纳米诊断探针，通过体内外实验来调整不同诊断探针的比例，验证纳米探针的成像功能，以期实现对肿瘤进行早期诊断

中文关键词： 多模态成像；肿瘤靶向；分子影像探针；纳米载体；pH敏感

英文摘要： Early diagnosis is one of the most effective methods for improving cancer cure rates, and multimodality molecular imaging is the most effective tool for cancer early and accurate diagnosis. Multi-modal nano-probes can solve the problem of the different ratio of different probes, but how to improve the cancer targeting and to enhance cancer penetration of nano probes are still need to solve. In this project polyamidoamine (PAMAM) dendrimer which has a large number of amine groups on the surface will be conjugated to superparamagnetic iron oxide nanoparticles (SPIOs) coated by silica to prepare PAMAM-Fe3O4@SiO2 superparamagnetic nano-system. A novel peptide LCTP which has been screened by phage display in vivo in our early experiments as cancer targeting agent, and tumor-penetrating peptide iRGD and poly(β-amino ester)(PAE) which can reverse its charge with the change of pH will be conjugated to the nano system to form intelligent dual-targeting and high penetrating nano-carrier. The nano-carrier will be labeled with fluorescent molecule Cy7 and radionuclide 131I to synthesize cancer multimodality nano diagnostic probes which can be used for Optical Imaging (OI), Radionuclide Imaging and Magnetic Resonance Imaging (MRI). The ratio of different probes will be adjusted by in vitro and in vivo experiments, the function of cancer imaging and cancer penetration of nano-probe will also be studied. By completion of this project we hope the cancer early diagnosis and cancer cure rates can be improved.

英文关键词： multi-modality imaging;cancer targeting;molecular imaging probe;nanocarrier;pH-sensitive