中文摘要
既能透过血脑屏障又能进一步靶向中枢神经系统的双重靶向药物递送系统对于病毒引起的中枢神经系统感染类疾病的诊断和治疗有着重要的意义。本课题拟在前期“基于病毒结合肽介导的药物靶向转运体系”获得成功的基础上,以乙脑病毒表面蛋白结合肽为靶向分子,并将其修饰至外泌体表面。;利用改造后的外泌体包载抗乙脑病毒药物,构建具有双重主动脑靶向的递送系统。借助病毒能主动穿越血脑屏障以及嗜神经细胞靶向性的特性,通过多肽分子与感染乙脑病毒动物体内的病毒颗粒特异性结合,在病毒感染神经细胞的同时,介导药物穿越血脑屏障并递送至病毒感染中枢神经系统中,提高药物对乙型脑炎的治疗效果。借此探讨中枢神经系统病毒感染类疾病的双重靶向药物递送新策略,为中枢神经系统病毒感染类疾病的靶向治疗提供新思路。
英文摘要
The dual targeting drug delivery system, which targets both the blood-brain barrier (BBB) and the central nervous system (CNS), is important for the diagnosis and treatment of virus infection in CNS. Based on the success of the " the virus binding peptide mediated targeting delivery system ", our group proposed to use exosomes as a carrier, which were generated by engineering the imDCs to express lysosomal-associated membrane protein 2 (Lamp2), fused with the encephalitis virus surface protein binding peptide. The modified exosomes were loaded with antiviral drugs for Japanese encephalitis virus (JEV), so as to build a dual active brain targeting delivery system. This delivery system, through the ability of the virus to cross the blood-brain barrier and the neuroticism, specifically binds to the viral particles in the body of the infected JEV, mediating the drug through the BBB to the infected CNS, to improve the anti-JEV effect of drugs.The successful implementation of this study can explore the new dual target delivery strategy of virus infection in CNS, at the same time providing new ideas for the targeted therapy of CNS virus infection.
