脑肿瘤难治，与药物受血脑屏障限制，难以进入脑肿瘤病灶组织密切相关。打开血脑屏障，同步实施脑肿瘤的药物主动靶向，是实现脑肿瘤高效安全治疗的有效途径。本项目拟通过对脑肿瘤病理学过程、血脑屏障信号通路干预、以及药物递释系统治疗前后的脑脊液组学特征谱研究，发现并筛选打开血脑屏障信号通路，探索脑肿瘤血脑屏障渗透性功能调控的分子机制。通过建立血脑屏障的细胞模型与脑肿瘤动物模型，研究药物首次治疗条件下调控病理性血脑屏障功能短期“恢复”的分子机制，通过组学研究进一步发现并优选新的信号通路及其激动剂，探索激动剂调控血脑屏障功能“破坏”的时效与量效关系，选择阿霉素、紫杉醇为模型药物，构建Angiopep-2多肽修饰、二硫键链接，具有肿瘤靶向及内环境GSH敏感释放功能的糖脂嫁接物胶束、纳米结构脂质体药物递释系统，研究“激动剂+药物递释系统”序贯给药治疗脑部肿瘤的可行性及安全性，为脑部肿瘤治疗提供新思路、新策略。

The treatment of brain tumor is seriously restricted by the blood brain barrier (BBB), which prevents the chemotherapeutics from penetrating into brain. Opening the BBB for brain tumor targeting therapy is an effective way to achieve brain tumor effective and safe treatment. This study intends to explore the molecular mechanism regulating BBB permeability, discovery and screen the signaling pathway regulating BBB function through the study of the pathological process of brain tumor, BBB functional intervention and the characteristics of cerebrospinal fluid before and after chemotherapy. We try to explore the mechanism of pathological BBB functional recovery after a single chemotherapy by the cell model of physiological and pathological BBB in vitro and intracranial tumor model in vivo, search and further optimize new signaling pathways and its agonist involved in BBB functional regulation, then explore the time-curve and dose-cure of agonist regulating BBB permeability increased. Doxorubicin and paclitaxel are considered as model drugs, we intend to establish angiopep-2 modified redox-responsive glycolipid-like copolymeric micelles and liposomes, further exploring the feasibility and safety of sequential administration of agonist and drug delivery systems in the treatment of brain tumors, and to provide new ideas and strategies for the treatment of brain tumors.