biostudies-literatureUnknown6(9)Wang WOxidative damage and neuroinflammation are the key features of central nervous system (CNS) injury. Inspired by the neuroprotective properties of neural stem cell-derived exosomes (NExo) and the reactive oxygen species (ROS) scavenging ability of selenium, we develop an advanced NExo bearing ultrasmall nano-selenium (∼3.5 nm) via lipid-mediated nucleation (SeNExo). In addition to maintaining the biological components of NExo, the resulting SeNExo exhibits a Se-O bond that dramatically enhances its ROS-scavenging performance. SeNExo penetrates the blood-brain barrier (BBB) via the apolipoprotein E and prolow-density lipoprotein receptor-related protein 1 (APOE_LRP-1) interaction. Through proteomics, microRNA (miRNA) omics, and single-nucleus RNA sequencing, we find that SeNExo can alleviateCell reports. Medicine102319https://www.ebi.ac.uk/biostudies/studies/S-EPMC12490213biostudies-literatureSelenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system.PMC12490213Tan HQin MZhang HWang DLi FWei WLyu CGuo PLi WLu GLi SWang WWang YZhao JZheng DMa GfalseSelenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system.Oxidative damage and neuroinflammation are the key features of central nervous system (CNS) injury. Inspired by the neuroprotective properties of neural stem cell-derived exosomes (NExo) and the reactive oxygen species (ROS) scavenging ability of selenium, we develop an advanced NExo bearing ultrasmall nano-selenium (∼3.5 nm) via lipid-mediated nucleation (SeNExo). In addition to maintaining the biological components of NExo, the resulting SeNExo exhibits a Se-O bond that dramatically enhances its ROS-scavenging performance. SeNExo penetrates the blood-brain barrier (BBB) via the apolipoprotein E and prolow-density lipoprotein receptor-related protein 1 (APOE_LRP-1) interaction. Through proteomics, microRNA (miRNA) omics, and single-nucleus RNA sequencing, we find that SeNExo can alleviate2025-01-01T00:00:00Z2025 Sep2026-06-04T01:51:13.592Z2026-05-04T03:14:09.966ZS-EPMC124902134088262310.1016/j.xcrm.2025.102319