Ischemic stroke is the leading cause of disability and death worldwide. Currently, the only proven treatment for ischemic stroke is restoring the cerebral blood supply. In addition, some of the tissue is damaged during the subsequent reperfusion because of the overproduction of reactive oxygen species (ROS). Furthermore, antioxidant therapies have shown promise in preclinical studies for the treatment of ischemia-reperfusion injury. However, their therapeutic efficacy has been limited because of their low bioavailability in brain. To resolve this issue, we synthesized ROS-responsive, fan-shaped dendrimer nanoparticles (NPs) and conjugated them with a blood-brain barrier (BBB)-targeting peptide, COG1410, and salvianic acid A (SA), which is an effective antioxidant in ischemic stroke. The BBB targeting peptide acts as a ligand of the nanocarrier system and penetrates the BBB through the endocytosis of the ligand receptor. The results showed that T-SA-NPs not only target and accumulate in the infarct area, they also reduce over 2 times of the infarct area and reverse the behavioral deficits in MCAO mice, which illustrates that these NPs have an effective therapeutic effect on the ischemic stroke. In addition, these NPs had no toxicity in any organs of the body. Importantly, the present study provides an alternative strategy for delivering antioxidants to the brain and achieving targeted therapy of ischemic stroke.

缺血性中风是世界范围内致残和死亡的主要原因。当前，对缺血性中风唯一有效的疗法是恢复脑血供。另外，由于活性氧（ROS）的过量产生，在随后的再灌注期间一些组织受到损害。此外，抗氧化剂疗法在临床前研究中显示出了治疗缺血再灌注损伤的前景。然而，由于它们在脑中的生物利用度低，它们的治疗功效受到限制。为解决此问题，我们合成了ROS反应性，扇形的树枝状大分子纳米颗粒（NPs），并将其与靶向血脑屏障（BBB）的肽COG1410和丹酚酸A（SA）偶联，后者是有效的抗氧化剂在缺血性中风。BBB靶向肽充当纳米载体系统的配体，并通过配体受体的内吞作用穿透BBB。结果表明，T-SA-NPs不仅靶向并聚集在梗塞区域，而且还减少了梗塞区域的2倍以上，并且逆转了MCAO小鼠的行为缺陷，这说明这些NPs对MCAO小鼠具有有效的治疗作用。缺血性中风。另外，这些NP对身体的任何器官都没有毒性。重要的是，本研究提供了将抗氧化剂输送到大脑并实现缺血性卒中靶向治疗的替代策略。它们还减少了梗塞面积的2倍以上，并逆转了MCAO小鼠的行为缺陷，这说明这些NP对缺血性中风具有有效的治疗作用。另外，这些NP对身体的任何器官都没有毒性。重要的是，本研究提供了将抗氧化剂输送至大脑并实现缺血性中风的靶向治疗的替代策略。它们还减少了梗塞面积的2倍以上，并逆转了MCAO小鼠的行为缺陷，这说明这些NP对缺血性中风具有有效的治疗作用。另外，这些NP对身体的任何器官都没有毒性。重要的是，本研究提供了将抗氧化剂输送到大脑并实现缺血性卒中靶向治疗的替代策略。