纳米药物在缺血性脑卒中靶向治疗中的研究进展

Research progress in nanomedicine for targeted therapy of ischemic stroke

在缺血性脑卒中(IS)发生过程中,血管系统血栓可导致脑组织缺血缺氧,产生炎症细胞因子引发脑组织损伤,缺血再灌注过程活性氧进一步引起应激性损伤。常规给药受制于血脑屏障的选择性通透作用和药物本身较低的生物利用度,对IS治疗效果不尽人意。纳米药物有望改变这一现状,其具有独特的作用机制,可穿越血脑屏障到达梗死灶周围,释放药物或治疗基因,发挥治疗作用。纳米药物通过抑制血小板聚集和增强溶栓药物的药效,溶解血栓增加缺血区供血;通过对抗炎症细胞因子,消除活性氧,削弱损伤反应;负载治疗基因调控神经干细胞分化过程,增加神经元的数量,诱导血管的发生,增强脑组织修复功能。纳米药物不但改善药动学和药效学,实现更有效的药物治疗,且可利用纳米成像技术实现IS治疗过程的实时监测和病情评估。

In case of ischemic stroke(IS),thrombus in the vascular system can cause ischemia and hypoxia in brain tissue,produce inflammatory cytokines and cause brain tissue damage,while reactive oxygen species during ischemia-reperfusion cause stress injury.Conventional drug administra⁃tion is limited by the selective permeability of the blood-brain barrier and the low bioavailability of the drug itself,and its therapeutic effect against IS is unsatisfactory.Nanomedicine is expected to bring hope in that it has a unique mechanism of action and can cross the blood-brain barrier to reach the periphery of the infarct,release drugs or therapeutic genes,and exert a therapeutic effect.Nanomedi⁃cine inhibits platelet aggregation,enhances the efficacy of thrombolytic drugs,dissolves thrombus,increases blood supply to ischemic areas,eliminates reactive oxygen species and weakens injury response by fighting inflammatory cytokines.Loaded therapeutic genes regulate the differentiation pro⁃cess of neural stem cells,increase the number of neurons,induce the occurrence of blood vessels,and enhance the repair function of brain tissue.Nanomedicines can not only improve pharmacokinetics and pharmacodynamics to achieve more effective drug treatment,but also use nanoimaging technology to achieve real-time monitoring and condition assessment of therapy.