PEI/5-FU修饰的功能性食管支架防止再狭窄研究

项目名称： PEI/5-FU修饰的功能性食管支架防止再狭窄研究

项目编号： No.U1504310

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 张琨

作者单位： 郑州大学

项目金额： 27万元

中文摘要： 晚期食管癌患者采用的支架植入姑息疗法常出现支架内再狭窄问题，主要由肿瘤细胞、炎症引起的肌成纤维细胞与上皮细胞过度增殖所致。前期工作发现多巴胺可以在金属支架表面形成稳定的有机-无机过渡层。与药物分子共价结合，有望阻抗肿瘤细胞、肌成纤维细胞、上皮细胞、炎症细胞等。本研究利用药物洗脱支架的基本原理，采用聚乙烯亚胺（PEI）与临床化疗药物5-氟尿嘧啶（5-FU），在317L不锈钢表面构建具有持续阻抗/杀伤细胞的修饰层，通过表层5-FU药物的缓释阻抗/杀伤周围细胞，PEI底层长期阻抗细胞的生长。利用FTIR、SEM、QCM、Western Blot、RT-PCR、体外细胞相容性、炎症抑制作用分析等进行功能层的表征与评价，探究PEI与5-FU阻抗/杀伤多种细胞的作用机制。该研究将为PEI/5-FU联合修饰防止食管支架内再狭窄提出新的策略与方法，为带瘤患者用管腔支架材料的功能化修饰提供科学依据。

中文关键词： 表面修饰；多功能表面；分子固定；药物洗脱涂层；抗增生

英文摘要： Palliative treatment of advanced esophageal cancer using stents is often along with the complications of stent restenosis, the problem is mainly caused by tumor cell growth, excessive proliferation of myofibroblasts and epithelial cells after inflammation. Prophase work found that dopamine can form the organic - inorganic transition layer on the surface of metal stents steadily. Thus it may covalently bind with drug molecules to form a stable functional layer, impeding/killing tumor cells, myofibroblasts and epithelial cells and inflammatory cells. Here, the basic technical principle of drug-eluting stents is referenced, using polyethyleneimine (PEI) and clinical chemotherapy drug 5 - fluorouracil (5 - FU) as impedance molecules. The surface modification of the scaffold material (such as 317 L stainless steel) can be made to construct the functional layer, which will impede/kill cells through the slow-releasing 5 - FU drugs and have the function of the impedance cell growth around a long time by PEI. The functional layer will be characterized and evaluated using FTIR, SEM, QCM-D, Western Blot, RT-PCR, in-vitro cell compatibility, inflammation inhibitory effect analysis, and the impedance/killing mechanism of PEI with 5 - FU can be explored. The study will put forward the new strategy and method for providing the PEI / 5 - FU combined modification to prevent esophageal stent restenosis, as well as provide scientific basis of functionalized modifications on lumen scaffolds for patients with tumor.

英文关键词： surface modification;multifunctional surface;molecules Immobilization;drug-eluting coatings;anti-hyperplasia