用于脑胶质瘤治疗的多靶点靶向脂质体联合给药系统的研究

脑胶质瘤是最常见的脑内恶性肿瘤，尚无令人满意的药物治疗方法。本课题针对脑胶质瘤存在血-脑屏障（BBB）、普通肿瘤细胞和肿瘤干细胞，拟采用两种脑胶质瘤靶向脂质体递药系统联合给药，提高药物入脑量，共同靶向打击瘤体中普通肿瘤细胞和肿瘤干细胞，实现高效低毒的治疗目标，为临床治疗脑胶质瘤提供有益思路。脑胶质瘤靶向脂质体递药系统（一）采用脑靶向分子CDX、脑胶质瘤细胞靶向分子c(RGDyK)共修饰脂质体递药系统，赋予其跨BBB、靶向普通脑胶质瘤细胞的功能，携带紫杉醇靶向打击普通脑胶质瘤细胞；脑胶质瘤靶向脂质体递药系统（二）采用脑靶向分子CDX、脑胶质瘤干细胞靶向分子AQYLNPS类似肽共修饰脂质体递药系统，赋予其跨BBB、靶向脑胶质瘤干细胞的功能，携带硼替佐米靶向打击脑胶质瘤干细胞；利用不同靶点靶向优势互补，开展两种靶向脂质体递药系统联合给药，优化给药方案，实施对脑胶质瘤深度打击。

Glioma is one of the most common types of brain tumor. Although extensive efforts have been made to improve efficacy of chemotherapy, there is no effective treatment currently available for this malignant disease. In order to treat glioma as thoroughly and safely as possible, it is necessary to kill both non-tumorigenic glioma cells and glioma stem cells at the same time. To this end, co-delivery of multi-tageted liposomal systems is proposed to target brain-blood barrier (BBB), normal glioma tumor cells as well as glioma stem cells.These glioma targeted liposomal systems include: 1)brain-targeted moiety-CDX and glioma-targeted moiety-c(RGDyK) modified liposomes that will be utilized to deliver chemotherapeutics-paclitaxel to kill nronal glioma cells; 2)brain-targeted moiety-CDX and glioma stem cell-targeted moiety-AQYLNPS modified liposomes that will be utilized to deliver bortezomib (BTZ) to kill glioma stem cells.Optimized co-delivering regimen of these two targeted liposomal systems will take fully advantage of their multi-targeted effects, thus eventually leading to a new direction in the treatment of gliomas.