{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:55:34Z","timestamp":1793073334048,"version":"4.5.0"},"reference-count":75,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272499"],"award-info":[{"award-number":["82272499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key program of Taizhou Clinical Medical College","award":["TZKY20220302"],"award-info":[{"award-number":["TZKY20220302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The recovery of neurological function following spinal cord injury (SCI) is primarily constrained by two core pathological mechanisms: neuroinflammation and impaired tissue regeneration. While extracellular vesicles (EVs) have emerged as a promising therapeutic approach, their clinical translation remains limited by the inherent low bioactivity of natural EVs and suboptimal targeting efficiency at lesion sites. In this study, we developed a targeted EV delivery system with synergistic therapeutic potential, termed C-A\/R-EVs, through a multidimensional engineering strategy. Specifically, the system leverages the blood-spinal cord barrier-penetrating ability of Angiopep-2 and the pathologically neovascular targeting capability of RGD to achieve precise localization in the SCI region. Additionally, a curcumin pretreatment strategy is employed to enhance the anti-inflammatory and neuroregenerative properties of the EVs. SnRNA-seq reveals that C-A\/R-EVs reprogram microglia from a pro-inflammatory phenotype to a reparative phenotype, effectively suppressing neuroinflammation and promoting neural repair. Mechanistically, C-A\/R-EVs facilitate axonal regeneration through enhancing the phagocytosis of myelin debris via reparative microglia, while simultaneously reducing the presence of inflammatory microglia to mitigate postinjury neuroinflammation. Moreover, C-A\/R-EVs contribute to the restoration of the blood-spinal cord barrier. This study provides new insights into the design and fabrication of engineered EVs to synergistically enhance spinal cord repair through multimodal mechanisms.<\/jats:p>","DOI":"10.1021\/acsnano.5c08573","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T22:28:47Z","timestamp":1755901727000},"page":"31551-31571","source":"Crossref","is-referenced-by-count":16,"title":["Multidimensional\nEngineering of Extracellular Vesicles\nfor Targeted Delivery and Microglial Reprograming in Spinal Cord Injury\nRepair"],"prefix":"10.1021","volume":"19","author":[{"given":"Wu","family":"Xiong","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University , , 300 Guangzhou Road , , ,","place":["Nanjing, Jiangsu, China, 210029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhao","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University , , 300 Guangzhou Road , , ,","place":["Nanjing, Jiangsu, China, 210029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , , ,","place":["Nanjing, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , 366 Taihu Road , , ,","place":["Taizhou, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , , ,","place":["Nanjing, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiran","family":"Chan","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , , ,","place":["Nanjing, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , , ,","place":["Nanjing, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University , , 300 Guangzhou Road , , ,","place":["Nanjing, Jiangsu, China, 210029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6503-7891","authenticated-orcid":true,"given":"Guang","family":"Kong","sequence":"additional","affiliation":[{"name":"Fourth Military Medical University , , , ,","place":["Xi\u2019an, Shaanxi, China, 710032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"Tang","sequence":"additional","affiliation":[{"name":"Nanjing Medical University , , 300 Guangzhou Road , , ,","place":["Nanjing, Jiangsu, China, 210000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-2028","authenticated-orcid":true,"given":"Jin","family":"Fan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University , , 300 Guangzhou Road , , ,","place":["Nanjing, Jiangsu, China, 210029"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"issue":"1","key":"2026093015095884900_cit1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-023-01477-6","article-title":"Spinal cord injury:\nmolecular mechanisms and therapeutic interventions","volume":"8","author":"Hu","year":"2023","journal-title":"Signal Transduction Targeted Ther."},{"key":"2026093015095884900_cit2","doi-asserted-by":"publisher","first-page":"102598","DOI":"10.1016\/j.arr.2024.102598","article-title":"Global, regional, and national burden of spinal cord\ninjury from 1990 to 2021 and projections for 2050: A systematic analysis\nfor the Global Burden of Disease 2021 study","volume":"103","author":"Lu","year":"2025","journal-title":"Ageing Res. Rev."},{"issue":"1","key":"2026093015095884900_cit3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00018-024-05186-3","article-title":"Deubiquitinase\nUCHL1 promotes angiogenesis and blood-spinal cord barrier function\nrecovery after spinal cord injury by stabilizing Sox17","volume":"81","author":"Wang","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"2026093015095884900_cit4","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.bioactmat.2024.04.015","article-title":"Functional biomaterials for modulating the dysfunctional\npathological microenvironment of spinal cord injury","volume":"39","author":"Ma","year":"2024","journal-title":"Bioact. 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