双靶向多功能纳米基因传递载体在鼻咽癌生物治疗中的作用及机制研究

项目名称： 双靶向多功能纳米基因传递载体在鼻咽癌生物治疗中的作用及机制研究

项目编号： No.81201764

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 郝秀华

作者单位： 吉林大学

项目金额： 23万元

中文摘要： 我国是全世界鼻咽癌发病率最高的国家之一，放疗是目前主要治疗手段五年生存率只有50%左右。本项目在前期工作基础上，设计和构建一种双靶向多功能纳米基因传递载体，能够高效靶向传递HSV-TK自杀基因进入鼻咽癌细胞核，通过直接和旁观效应特异性杀死肿瘤细胞；同时载体上嵌合仙台病毒F蛋白和共刺激分子B7-1蛋白，能够通过招引-活化效应激活CD4+T细胞和CD8+CTL，增强机体的抗肿瘤免疫效应，抑制肿瘤细胞的免疫逃逸，从而降低鼻咽癌复发及转移。鼻咽癌靶向肽和肿瘤特异启动子的双重靶向控制，使其具有更好的安全性，降低对机体的毒副作用，改善患者的生存质量。上述载体的构建和相应的机制研究将为探寻安全有效的治疗鼻咽癌生物治疗新方法提供依据和参考，具有重要的科学意义和潜在的实用价值。

中文关键词： 鼻咽癌；双靶向；多功能；基因传递载体；选择性肿瘤杀伤

英文摘要： Nasopharyngeal carcinoma is endemic, which has the highest incidence rates in China. Currently, radiotherapy is the mainstay treatment, achieving a 5-year overall survival of about 50%. Based on our previous work, this project aims to design and construct a multifunctional double-targeting nano-carrier system for gene delivery. The system can efficiently target the nasopharyngeal carcinoma cell and deliver HSV-TK suicide gene into nucleus, followed by cancer cell-killing in direct and bystander effects. The Sendai virus F protein and co-stimulating B7-1 protein carried on the surface of the nano-carrier can strengthen anti-tumor immunological efficiency, and inhibit escape of cancer cell from immune system through activating CD4+T and CD8+T cells. And as a result, this will decrease the possibility of relapse and transfer of cancer cells. The double-targeting control, mediated by nasopharyngeal carcinoma cell-targeting peptide and special promoter for tumor, will have the following properties: more safety, lower toxicity, better quality of life. This study will be a fundamental stone for nasopharyngeal carcinoma biotherapy, and is meaningful and valuable in the future.

英文关键词： Nasopharyngeal carcinoma；dual-targeting；multifunction；gene delivery vectors；tumor-selective killing