多功能金纳米棒诊疗系统在肿瘤靶向与光热治疗以及肿瘤成像中的研究

项目名称： 多功能金纳米棒诊疗系统在肿瘤靶向与光热治疗以及肿瘤成像中的研究

项目编号： No.21204069

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 高分子科学

项目作者： 肖玉玲

作者单位： 武汉大学

项目金额： 25万元

中文摘要： 本项目旨在设计一种基于金纳米棒的兼具诊断与治疗的多功能肿瘤靶向纳米递释系统，目的是同时实现分子诊断试剂和抗肿瘤药物的肿瘤靶向递释，同步对肿瘤进行诊断与治疗。该多功能纳米体系的结构以金纳米棒做为结构的主体，在其表面共价连接聚乙二醇（PEG）亲水链，在PEG的外端用靶向于整合素受体的cRGD环肽来实现体系的肿瘤靶向性，同时在PEG链上连接双功能螯合剂1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)，用正电子核素64Cu (t1/2: 12.7 h)进行标记，用于肿瘤的PET分子显像；此外，通过具有pH敏感性的腙键共价连接肿瘤治疗药物阿霉素（DOX）于金纳米棒上，由于金纳米棒独特的近红外吸收能力,本课题将有望协同肿瘤的化疗和光热治疗于一体。本课题将通过系统性的细胞及分子生物学实验考察对构建的靶向纳米递送系统的的肿瘤靶向性和肿瘤治疗效果。

中文关键词： 纳米载体；肿瘤靶向；正电子发射断层扫描成像；光热治疗；阿霉素

英文摘要： Cancer continues to be one of the world's most devastating diseases, with more than 10 million new cases each year. Nanotechnology provides extraordinary opportunities to address these challenges as nanocarriers can offer both passive and active targeting abilities towards cancerous tissues/cells. The current focus of nanomedicine is to develop multifunctional tumor-targeting drug/agent nanocarriers, including those capable of co-delivering anti-cancer drugs and imaging contrast agents which are termed cancer theranostics (i.e., combined therapy and diagnostics), thereby providing a more effective and multimodality approach in cancer management. In this proposal, a multifunctional gold nanorod (GNR)-based nanoplatform for targeted anti-cancer drug delivery and positron emission tomography (PET) imaging of tumors will be developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) will be covalently conjugated onto PEGylated GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and 64Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA)) will be conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Cellular

英文关键词： nanomedicine；tumor targeting；positron emission tomography imaging；photothermal therapy；Doxorubicin