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Clinical evidence linking high neutrophil counts to SCI severity underscores the need for precision immunomodulation. Herein, we report T\u2010H151, a smart, bio\u2010responsive nanoplatform designed to suppress neuroinflammation and enhance functional recovery via selective inhibition of the STING signaling pathway. T\u2010H151 consists of a liposomal carrier encapsulating the STING inhibitor H151, surface\u2010functionalized with a modular peptide design: a neutrophil elastase\u2010binding peptide (NEBP) for active hitchhiking, an MMP9\u2010responsive linker for site\u2010specific activation, and a neuron\u2010targeting peptide (TET) for enhanced cellular uptake. This architecture facilitates efficient neutrophil\u2010mediated transport to the lesion site, followed by MMP9\u2010triggered, precision release of H151 within the neuronal microenvironment. In SCI mouse models, T\u2010H151 significantly improves motor function and preserves blood\u2013spinal cord barrier integrity. Mechanistically, T\u2010H151 suppresses the STING axis, inhibits microglial\/macrophage activation, and reduces pro\u2010inflammatory cytokines (IL\u20101\u03b2, TNF\u2010\u03b1). Transcriptomic analysis further confirms a profound downregulation of the NF\u2010\u03baB and JAK\u2013STAT inflammatory pathways. Collectively, this targeted nanoplatform offers a transformative, bio\u2010responsive strategy for mitigating neuroinflammation and promoting therapeutic outcomes in spinal cord repair.<\/jats:p>","DOI":"10.1002\/adhm.71742","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:49:41Z","timestamp":1789962581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil\u2010Hitchhiking and Microenvironment\u2010Responsive Cascade Nanoparticles for STING Inhibition and Spinal Cord Injury Repair"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaofeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Fourth Affiliated Hospital of Zhejiang University School of Medicine, and International School of Medicine International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianhui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Han","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional and Western Medicine Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ji","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional and Western Medicine Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwei","family":"Jie","sequence":"additional","affiliation":[{"name":"Affiliated Gaozhou People's Hospital Guangdong Medical University  Maoming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Gaozhou People's Hospital Guangdong Medical University  Maoming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Shan","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional and Western Medicine Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Li","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional and Western Medicine Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-5381","authenticated-orcid":false,"given":"Qingchun","family":"Mu","sequence":"additional","affiliation":[{"name":"Affiliated Gaozhou People's Hospital Guangdong Medical University  Maoming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9517-1325","authenticated-orcid":false,"given":"Longguang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Center for Regenerative and Aging Medicine The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine International Institutes of Medicine Zhejiang University  Yiwu 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