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Targeting hyperactivated microglia and regulating polarization are promising strategies for treating the disease. Mesenchymal stem cell (MSC) transplantation is proven to be an effective treatment due to its immunomodulatory and regenerative properties. However, the low efficiency of cell migration and integration of MSCs remains a major obstacle to clinical use. The goal of this study is to develop a nanodelivery system that targets hyperactivated microglia and inhibits their release of proinflammatory factors, to achieve durable neuroprotection. This approach is to engineer extracellular vesicles (EVs) isolated from MSC, modify them with a cyclic RGD (cRGD) peptide on their surface, and load them with an antagonist of the IL\u20101 receptor, anakinra. Comparing with non\u2010engineered EVs, it is observed that engineered cRGD\u2010EVs exhibit an increased targeting efficiency against hyperactivated microglia and strongly protected photoreceptors in experimental RD cells and animal models. This study provides a strategy to improve drug delivery to degenerated retinas and offers a promising approach to improve the treatment of RD through targeted modulation of the immune microenvironment via engineered cRGD\u2010EVs.<\/jats:p>","DOI":"10.1002\/smll.202302962","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T02:10:53Z","timestamp":1690769453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Engineered Extracellular Vesicles for Delivery of an IL\u20101 Receptor Antagonist Promote Targeted Repair of Retinal Degeneration"],"prefix":"10.1002","volume":"19","author":[{"given":"Yizong","family":"Liu","sequence":"first","affiliation":[{"name":"Eye Center Renmin Hospital of Wuhan University  Wuhan Hubei 430060 P. R. 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