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Stimuli\u2010responsive nanomedicine has emerged as a promising non\u2010invasion technology, which enhances drug delivery and promotes functional recovery following SCI. Considering the multiple progressive pathological events and the blood spinal cord barrier (BSCB) associating SCI, a microenvironment self\u2010adaptive nanoparticle (custom\u2010designed with rabies virus glycoprotein 29\u2010RVG29 and hyaluronic acid\u2010HA, RHNP) capable of consistently crossing the BSCB and selectively targeting inflammatory cells and neural cells based on different stages of SCI are developed. The data indicated that RHNP can effectively traverse the BSCB through RVG29, and adaptively modulate cellular internalization by selectively exposing either HA or RVG29 through diselenide bonds, depending on pathological reactive oxygen species (ROS) signals. Furthermore, curcumin is loaded into RHNP (RHNP\u2010Cur) to improve motor function and coordination of hind\u2010limbs in a traumatic SCI mouse model. This study finds that RHNP\u2010Cur exhibited inhibitory effects on the inflammatory cascade originating from M1 microglia\/macrophages and neurotoxic astrocytes, and protected neural cells from inflammation\u2010induced apoptosis during nerve regeneration. Collectively, the work provides a microenvironment self\u2010adaptive nanomedicine which enables efficient microinvasive treatment of SCI.<\/jats:p>","DOI":"10.1002\/adma.202307624","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T04:23:28Z","timestamp":1730348608000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Microenvironment Self\u2010Adaptive Nanomedicine Promotes Spinal Cord Repair by Suppressing Inflammation Cascade and Neural Apoptosis"],"prefix":"10.1002","volume":"36","author":[{"given":"Dingfei","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Orthopedics Chinese PLA General Hospital  28 Fuxing Road, Haidian District Beijing 100853 China"},{"name":"Department of Orthopedics The Fourth Medical Center Chinese PLA General Hospital  51 Fucheng Road, Haidian District Beijing 100048 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Nanoscience and Engineering University of Chinese Academy of Sciences  Beijing 100049 China"},{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety &amp; 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