量子点标记基于功能化磷脂的溶瘤病毒及其与肿瘤细胞相互作用研究

项目名称： 量子点标记基于功能化磷脂的溶瘤病毒及其与肿瘤细胞相互作用研究

项目编号： No.21275111

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 林毅

作者单位： 武汉大学

项目金额： 80万元

中文摘要： 溶瘤病毒是指能够特异性地侵染肿瘤细胞并在其内复制，导致肿瘤细胞死亡后释放大量子代病毒，进而再次攻击其它肿瘤细胞的一类病毒。基于溶瘤病毒可以建立新颖的癌症（恶性肿瘤）治疗方法，但目前其制备大多采用基因工程技术，操作繁琐。项目旨在基于我们前期提出的宿主细胞中功能化磷脂"自然嵌合"标记囊膜病毒新策略，建立构建溶瘤病毒的通用新方法及基于量子点单颗粒示踪技术研究溶瘤病毒与细胞相互作用的新方法。拟修饰病毒囊膜中普遍大量存在的磷脂的亲水部分来获得几类功能化磷脂，利用其在宿主细胞中标记囊膜病毒并实现病毒对肿瘤细胞的靶向识别，构建新型溶瘤病毒。在此基础上，拟采用量子点标记所构建的溶瘤病毒的非侵染决定部位，建立无损的量子点标记溶瘤病毒新方法，并基于单颗粒示踪技术研究溶瘤病毒与肿瘤细胞及相应正常细胞的相互作用。相关结果将为采用化学方法调控病毒靶向性及构建新型溶瘤病毒提供依据，为利用溶瘤病毒治疗癌症提供新的可能。

中文关键词： 病毒；磷脂；量子点；肿瘤；靶向

英文摘要： Oncolytic virus (OV) is the virus that can selectively infect and replicate in cancer cells, with minimal destruction of non-neoplastic tissue. Due to its replication, a large number of newly born virons are released on the rupture of tumor cells, and then they are able to attack other tumor cells again. Based on OV, promising methods for cancer therapy can be established. Although some OVs are in their clinic stage of development, most methods for the preparation of OV are based on the genetic engineering approach, causing the complication in operation, prone to mutation. To make things worse, there is still potential toxicity with current OV. Herein, the project is planned to develop a universal method to design and prepare OVs based on phospholipids and enveloped virus, so that the targeting of OVs and the reduction of their toxicity can be realized. First, several new types of functional phospholipids will be designed and synthesized. Second, based on the pre-established "natural fusion" approach, enveloped viruses as well as their host cells will be modified with the above-mentioned functional phospholipids. Third, the targeting of the as-prepared new OVs will be inspection and regulated with the phospholipids. Fourth, the as-prepared new OVs will be labeled with quantum dots (QDs) at the cost of losses in

英文关键词： virus；phospholipids；quantum dots；tumor；targeting