肿瘤酶靶向及高穿透性纳米粒子/温敏凝胶一体双相系统对胃癌腹腔转移的疗效评价

项目名称： 肿瘤酶靶向及高穿透性纳米粒子/温敏凝胶一体双相系统对胃癌腹腔转移的疗效评价

项目编号： No.81472216

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： 李茹恬

作者单位： 南京大学

项目金额： 80万元

中文摘要： 腹腔转移是胃癌最重要的不良预后因素，腹腔灌注化疗（IPC）已逐渐成为胃癌腹腔转移的主要治疗手段，提高IPC疗效是胃癌临床最迫切的需求。申请人前期在国科金青年项目中，采用FDA批准的高分子聚乙二醇及聚己内酯（PEG、PCL）构建了可同时抑制肿瘤干细胞及肿瘤细胞的明胶酶靶向盐霉素-多西紫杉醇纳米粒子。本项目拟在此基础上建立酶靶向及高穿透性一体双相复合载药系统，用于胃癌IPC。基于对PEG与PCL的嵌段结构及分子配比的设计（一体），该系统由靶向纳米粒子及25℃左右为液态，37℃时为固态的温敏纳米凝胶两部分构成（双相），修饰以最新发现的肿瘤穿透及血管亲和肽iNGR。在前期建立的裸鼠胃癌腹腔转移模型上，着重研究复合系统在抑制胃癌干细胞，提高局部药物浓度、促进药物渗透、降低毒性等方面的优势，为胃癌腹腔转移的治疗提供新思路，也为我国潜在自主知识产权的新型靶向载体药物的研制及向临床过渡提供科学依据。

中文关键词： C07_胃肿瘤；靶向药物投递；纳米粒子/凝胶；腹腔灌注化疗；肿瘤干细胞

英文摘要： Peritoneal metastasis is the most important prognostic factor in gastric cancer patients. Recently, intraperitoneal chemotherapy (IPC) has become the mainstream of treatment of gastric cancer with peritoneal metastasis and to improve the effectiveness of IP chemotherapy is clinincally urgently needed. Based on the previous nantional science foundation, we established polyethylene glycol (PEG)-poly (ε-caprolactone) (PCL)-gelatinase-responsive salinomycin-docetaxel nanoparticles to simultaneously inhibit cancer stem cell (CSC) and non-CSC cancer cells. In the current work, we plan to establish the gelatinase-responsive and tumor-penetrating double phasenanocomplex for IPC of gastric cancer. This nanocomplex composes of PEG-PCL gelatinase-responsive salinomycin-docetaxel naoparticles, PEG-PCL thermosensitive nanohydrogel which is aqeous at 25℃ and solid at 37 ℃, and tumor-penetrating, tumor-vessel homing peptide iNGR. Then the effectiveness of this nanocomplex was studied on nude mice gastric cancer peritoneal metastasis model, focusing on the inhibiton of CSC, increasing of local drug concentration, promotion of drug penetration, decrease of toxicities. We hope that this research program will provide scientific evidence to develop new targeted drug carriers and transit them to clinical application.

英文关键词： gastric cancer;targeted drug delivery;nanoparticles/hydrogel;intraperitoneal chemotherapy;cancer stem cell