V-M双肽介导的载自杀基因纳米粒靶向杀伤胶质瘤的体内体外实验及其机制研究

It is expected that gene therapy will become one of powerful adjuvant methods of conventional therapies. There have been lots of studies on the “Warhead” (gene), but a few on the “Rocket” (gene-carrier). There is still quite difficult to kill glioma cells effectively and specially without harming neural cells and other normal cells, which is worth studying. We successfully constructed the targeting gene-carrier which effectively and specially transfected glioma cells in our previous studies. This project will construct vectors with V-peptide, M-peptide, poly-L-lysine and polyethylene glycol, which will be used to make targeting nanoparticles loaded with suicide gene Ec-CD. The physical and chemical characteristics of nanoparticles will be examined. Several glioma cell lines and primary glioma cells extracted from glioma tissues of patients will be transfected with the nanoparticles, whose transfection ability, security and mechanisms will be examined from many levels of pharmacy, molecule, cell and animal. This project will expect that our targeting nanoparticles loading with suicide genes may safely, specially and effectively kill glioma cells, which may provide a new tool for gene therapy of gliomas.

基因治疗有望成为胶质瘤传统治疗强力辅助手段之一，这颗导弹的弹头（目的基因）已有许多研究，但运载火箭（载体）尚有待完善。如何做到高效、特异地杀伤胶质瘤，同时避免伤害神经细胞等正常细胞，是热点，也是难点。我们前期研究成功构建了靶向因子V肽介导的基因载体，并高效、特异地转染了胶质瘤细胞。本课题以V肽、破膜因子M肽、多聚赖氨酸及聚乙二醇共同构建载体，使之搭载自杀基因Ec-CD，成为靶向载基因纳米粒，考察其理化特性，转染若干胶质瘤细胞系及取自病人胶质瘤组织的原代胶质瘤细胞，再予以5-FC给药，通过药剂学、分子学、细胞学、动物学等多学科多技术研究纳米粒在体外及体内特异杀伤胶质瘤细胞的能力，探索其作用机制，并评估其安全性。本课题重点在于构建安全、靶向、高效地杀伤胶质瘤的新式载体系统，预期可能为胶质瘤的基因治疗提供新思路。