Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis

• Published in: Journal of nanobiotechnology 2023-03, Vol.21 (1), p.109-109, Article 109
• Main Authors: Wang, Yong, Niu, Huicong, Li, Luyu, Han, Jing, Liu, Zhuohang, Chu, Min, Sha, Xianyi, Zhao, Jing
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Brain; Brain - metabolism; Brain injury; Brain Ischemia - metabolism; Care and treatment; Carotid arteries; Cell death; Cell organelles; Cerebral ischemia; CHAC1; Datasets; Deprivation; Drug delivery systems; Drugs; Ethylenediaminetetraacetic acid; Exosomes; Exosomes - metabolism; Ferroptosis; Genes; Head injuries; Health aspects; Immunofluorescence; Injuries; Injury analysis; Intranasal administration; Ischemia; Ischemic Stroke - metabolism; Laboratory animals; Localization; Mesenchymal stem cells; Mice; MicroRNA; MicroRNAs; MicroRNAs - metabolism; Neurons; Neurons - metabolism; Pharmaceutical research; Reperfusion; Reperfusion injury; Reperfusion Injury - metabolism; Review boards; Software; Stem cells; Stroke; Surgery; Vehicles; Veins & arteries
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-01862-x

Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen-glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC-Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury.