Zhao Yijing, Song Cong, Wang Haijun, Gai Chengcheng, Li Tingting, Cheng Yahong, Liu Junjie, Song Yan, Luo Qian, Gu Bing, Liu Weiyang, Chai Liwei, Liu Dexiang, Wang Zhen
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, Shandong 250117, P.R. China.
Biomater Res. 2024 Sep 18;28:0079. doi: 10.34133/bmr.0079. eCollection 2024.
Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke.
缺血性中风是一种毁灭性疾病，也是全球主要的死亡原因之一。活性氧的过度产生和炎症反应会导致缺血性损伤后的继发性损伤。具有强大抗氧化应激特性的纳米酶对缺血性损伤具有治疗潜力。然而，纳米酶在神经元线粒体中的积累不足阻碍了它们的应用。在此，我们构建了聚多巴胺包覆的普鲁士蓝纳米颗粒（PB@PDA NPs），以实现对缺血性中风神经元线粒体的靶向作用，具有抗氧化和抗炎特性。给药后，与PB NP组相比，观察到PB@PDA NPs在脑中的积累要高得多。此外，在新生小鼠缺氧缺血（HI）损伤后，PB@PDA NPs比PB NPs更有效地减轻了脑梗死。PB@PDA NPs在体内和体外主要与神经元线粒体共定位。除了减轻氧化应激外，PB@PDA NPs还抑制神经元凋亡并对抗炎症，这有效地促进了HI小鼠的短期和长期功能恢复。此外，通过尾静脉注射在成年缺血小鼠中也发现了PB@PDA NPs的治疗效果。总的来说，这些发现表明，通过系统注射的PB@PDA NPs在神经元线粒体中积累，对缺血性中风有益。
