XEO2mini核酸识体靶向的DNA 自组装纳米诊疗系统：构建及术中成像介导下前列腺癌细胞清除的问题研究

项目名称： XEO2mini核酸识体靶向的DNA 自组装纳米诊疗系统：构建及术中成像介导下前列腺癌细胞清除的问题研究

项目编号： No.81471779

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： 肖泽宇

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 手术切除肿瘤是当前最有效的治疗前列腺癌症的方法。其治愈效果取决于在术中能否准确地辨析肿瘤边界，及能否完全的清除残余的肿瘤细胞。本项目中，我们拟构建一个DNA自组装，核酸识体靶向的纳米诊疗系统，其整合(1)拉曼影像组分，用于高灵敏的检测肿瘤边界及残余肿瘤细胞，从而指导手术切除；（2）新靶向分子(XEO2mini核酸识体)，用于选择性地识别前列腺癌细胞；(3)金纳米棒，用于提供近红外光控制的光热及化学联合治疗，实现彻底地杀伤残余肿瘤细胞。重要的是，这个多功能的纳米诊疗系统可以通过一步DNA自组装合成，从而能够精确地调整其理化性质，也利于高重复性的大批量地合成该纳米粒子。我们将研究此纳米系统的诊断治疗作用，探讨靶向及光热增敏化疗机理，研究其非靶向作用机制。如果成功，该纳米诊疗系统将有望为术中前列腺癌的根治提供新思路。

中文关键词： DNA；自组装；诊疗一体化；纳米医学；核酸识体；肿瘤靶向治疗

英文摘要： Surgical resection of tumor tissue is considered to be the most effective strategy for late-stage prostate cancer treatments; however, its efficacy is limited due to the difficulties in accurately delineating tumor margins and in radically resecting tumor cells. In this proposal, we aim to develop a DNA-self assembled, aptamer targeted theranostic nano-platform that integrates (i) Raman imaging component for sensitive detection of tumor margins and residual cells, (ii) novel targeting molecules (XEO2mini aptamer) for cancer-cell specific recognition, and (iii) gold nanorod component, which enables near-infrared light trigged thermo-chemo combinational therapy for complete removal of residual tumor cells. Importantly, this multifunctional nano-platform can be synthesized via a DNA-assembled process, which facilities fine tune of the surface biophysicochemical properties of nanoparticles in a reproducible manner, and allows for a scaled-up process for future clinical translation. We will investigate the toxicity, biodistribution, action mechanism and theranostic efficacy of this DNA-assembled nano-platform in cell-based assay and/or orthotopic metastasis prostate tumor models. If successful, this theranostic platform would substantially improve the efficacy of surgery-based prostate cancer treatment, thereby significantly decreasing the risk of prostate cancer recurrence; this project will lay the groundwork for wider applications of nanotechnology-based surgical therapy for a myriad of other cancers and diseases.

英文关键词： DNA self-assembly;theranostics;nanomedicine;aptamer;targeted cancer therapy