血脑屏障（BBB）和血脑肿瘤屏障(BTB)的存在阻碍了药物对脑胶质瘤的有效治疗。如何在不影响BBB的前提下，选择性开放BTB，将药物靶向递送到脑胶质瘤组织？我们前期工作证明逆序D型缓激肽与聚合物胶束联合给药可增加药物在脑内蓄积，并显著延长原位脑胶质瘤模型动物的中位生存期。本申请项目将进一步研究逆序D型缓激肽与BTB上激肽受体B2的亲和性及其对体外BTB和BBB模型的开放效应是否有所不同、与逆序D型缓激肽联合给药后聚合物胶束在体外BTB和BBB模型上的转运行为是否有所差异、相对剂量、间隔时间和胶束粒径等因素是否影响聚合物胶束在脑肿瘤和正常脑组织的分布、以及评价逆序D型缓激肽与聚合物胶束联合给系统抗原位脑胶质瘤效果和初步生物安全性。这些研究将对寻找一种降低正常脑组织损伤的同时，有效提高药物抗脑胶质瘤作用的治疗策略具有理论和实际意义。

Due to the two special barriers of brain: blood-brain barrier (BBB) and blood-brain tumor barrier (BTB), the antitumor agents cannot through the hindrance into brain tumor tissues successfully to achieve the effective therapy. In order to decrease the damage of normal brain tissue, we need to look for a targeted strategy to deliver the antitumor agents to brain tumor by openning the BTB selectively without affecting the permeability of BBB. In previous studies, we demonstrated that co-administration of retro-inverso Bradykinin (RI-BK) can enhance the accumulation of drug loaded polymeric micelles in brain tumor and significantly prolonged the median survival time. Based on our studies, we plan to research the application of RI-BK in the treatment of brain tumor exhaustively from the following aspects: firstly, the affinity between RI-BK and bradykinin B2 receptor; secondly, the different respond between BBB and BTB in vitro after administration of RI-BK; thirdly, whether co-administration of RI-BK will influence the transport action of polymeric micelles in in vitro BBB and BTB model and the distribution of polymeric micelles in brain tumor and normal brain; fourthly, the influence of dosage, administration and particle size of polymeric micelles for the distribution of antitumor agents; finally, evaluation of the antitumor effect and toxicity on the drug delivery system that co-administration of RI-BK and polymeric micelles. This study will make contributions to finding a potential strategy for enhancing the efficacy of antitumor agents in theory and practice, to treat the brain tumor and decrease the damage of normal brain simultaneously.