氧化应激
缺血
活性氧
半影
再灌注损伤
胶束
细胞生物学
神经保护
药理学
神经科学
化学
医学
生物
生物化学
内科学
物理化学
水溶液
作者
Chao Li,Ya Ping Wu,Qinjun Chen,Yifan Luo,Peixin Liu,Zheng Zhou,Zhenhao Zhao,Tongyu Zhang,Boyu Su,Tao Sun,Chen Jiang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-09-13
卷期号:17 (18): 18164-18177
被引量:2
标识
DOI:10.1021/acsnano.3c05038
摘要
Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.
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