基于“导航式”氧化石墨烯纳米层构建的多功能光热联合化疗系统研究

项目名称： 基于“导航式”氧化石墨烯纳米层构建的多功能光热联合化疗系统研究

项目编号： No.81202485

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 侯琳

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 针对肿瘤单一化疗临床效果欠佳、传统联合治疗毒副作用较大的瓶颈，我们已成功开发单壁碳纳米管-抗癌药物转运系统，并证实其热疗联合化疗功效。在此基础上，本项目通过酰胺化反应，将光热特性、生物相容性更优的氧化石墨烯(GO)，与能特异性靶向肿瘤细胞表面CD44受体、并兼具辅助抗癌能力的多糖- - 透明质酸（HA）相连接，再采用透析法物理负载多烯紫杉醇（DTX），构建一种同时实现靶向输送及光热联合化疗的多功能纳米层。预期静脉注射该纳米层，可借助HA的靶向性导航至肿瘤部位，并发挥多种机制协同抑制肿瘤生长：DTX的细胞毒作用、GO的光热治疗作用及HA的辅助抗肿瘤作用。项目拟通过体外实验，观察其在近红外光照射下对肿瘤细胞的杀伤作用，以及与高表达CD44受体的肿瘤细胞结合能力；通过体内实验，以荷瘤小鼠为模型，观察其组织分布情况及释药特性，同时研究其在体抗肿瘤效果，评价本光热联合化疗系统的肿瘤靶向性和综合治疗效果。

中文关键词： 抗肿瘤；光热联合化疗；氧化石墨烯；透明质酸；靶向

英文摘要： To overcome the limitations of cancer single-agent therapy and decrease the side effects of traditional combination therapy, we have successfully developed anticancer drug-loaded single-walled carbon nanotubes system. Upon this promising drug delivery system for high treatment efficacy with minimal side effect, in this work, the covalent functionalization of graphene oxide (GO) with hyaluronic acid (HA) is successfully accomplished via a facile amidation process. The HA-grafted GO (HA-GO) can self-assemble into nanosheet and load a water-insoluble anticancer drug, Docetaxel (DTX), by dialysis method via π-π stacking and hydrophobic interactions. Owing to the capacity of near-infrared (NIR)-absorbing of GO, the ability to specifically bind to various cancer cells over-expressing CD44 as well as the synergetic antitumor activity of HA, and the cytotoxicity of DTX, this nanosheet can facilitate combined targeting chemotherapy and photothermal therapy in one system. In this study, the CD44 receptor-mediated endocytosis and photothermal effect under a NIR laser were investigated by cell experiment in vitro. Furthermore, in order to evaluate the dynamic behaviors and targeting ability of the DTX-loaded HA-GO nanosheet, the biodistribution, drug release profile and antitumor activity were also studied in vivo test. Con

英文关键词： antitumor；chemo-photothermal combination；graphene oxide；hyaluronic acid；targeting