隐形双靶纳米金的构建及其在肿瘤与相关新生血管协同靶向治疗中的应用研究

项目名称： 隐形双靶纳米金的构建及其在肿瘤与相关新生血管协同靶向治疗中的应用研究

项目编号： No.81460467

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 汪静

作者单位： 宁夏医科大学

项目金额： 47万元

中文摘要： 肿瘤早期靶向治疗非常重要，能够提高癌患者的存活率，靶向纳米金在肿瘤早期光热治疗中显示出独特优势和良好应用前景。但目前构建的靶向纳米金具有靶向单一性、体内循环不稳定以及与正常细胞相互作用等缺点，在体内靶向光热治疗中受到限制。根据我们前期的研究以及文献报道，利用实体瘤的酸性微环境或采用多重靶向模式，可有助于纳米靶向载体的在肿瘤位点的积累。本项目拟在PEG纳米金表面共价偶联双配体cRGDfK与叶酸，且在cRGDfK末端通过pH敏感腙键连接DTPA，构建稳定的隐形双重靶向纳米金，并对其稳定性、酸性实体瘤定点靶向以及在肿瘤细胞与其相关新生血管内皮细胞协同靶向作用进行评价。通过上述肿瘤酸性微环境与双靶模式的结合，探讨纳米金在肿瘤部位的靶向精准度以及靶向放大效率，为纳米金体内靶向光热治疗提供基础。

中文关键词： 纳米金；隐形；双靶；协同靶向；光热治疗

英文摘要： Targeting therapy of tumors in their early stages is crucial to increase the survival rate of cancer patients, targeting gold nanorods show the unique advantages and good prospect in the early photothermal therapy. However, the prepared targeting gold nanorods have the disadvantages of single targeting, unstable circulation and interaction with normal cells, which restrict the application of targeted therapy in vivo. According to our previous studies and literature reports, adopting acidic solid tumor microenvironment or multiple targeting mode can contribute to the accumulation of targeted nano-carrier in the tumor site. This project intends to bind covalently cRGDfK and folic acid to the surface of PEGlated gold nanorods, and conjugate a shielding molecule DTPA at the end of the cRGDfK by pH sensitive hydrazone to prepare stable stealth dual targeting gold nanorods. We will investigate the stability, designated targeting at acid solid tumor and synergistic targeted-photothermal therapy of tumor and Associated Angiogenesis using stealth dual targeting gold nanorods. Through associating the acidic solid tumor environment with the dual targeting mode, targeting precision and targeted amplification efficiency of gold nanorods are explored, which will provide research basis for targeting photothermal therapy in vivo.

英文关键词： gold nanorods;stealth;dual targeting;synergistic targeting;photothermal therapy