{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:25:04Z","timestamp":1787685904081,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide, with secondary injury recognized as a critical therapeutic target. Quercetin (QR), a natural flavonoid, exerts antioxidant and anti\u2010inflammatory effects by modulating the Nrf2\u2013Keap1 pathway and shows neuroprotective potential in various neurological disorders. In this study, network pharmacology analysis identified 496 overlapping targets of QR and TBI, further highlighting the pivotal role of the Nrf2\u2013Keap1 pathway in TBI treatment. However, the poor blood\u2013brain barrier (BBB) permeability and low bioavailability of QR hinder effective brain\u2010targeted delivery and limit its clinical translation. To address these challenges, we developed CAQK peptide\u2010modified, reactive oxygen species (ROS)\u2010responsive nanoparticles (C\u2010PPS\/Q), using PPS\n                    <jats:sub>120<\/jats:sub>\n                    as the core for targeted QR delivery. C\u2010PPS\/Q exhibited ROS\u2010triggered QR release, significantly enhanced HT22 cell uptake in\u00a0vitro, reduced ROS levels and apoptosis. In a TBI mouse model, C\u2010PPS\/Q specifically accumulated at the lesion site, prolonged the half\u2010life of QR, demonstrated excellent biocompatibility, preserved BBB integrity, attenuated neuroinflammation, inhibited aberrant Nrf2\u2010Keap1 pathway activation, and markedly improved neurological function. Collectively, C\u2010PPS\/Q nanoparticles effectively mitigate secondary brain injury after TBI and represent a promising brain\u2010targeted therapeutic strategy for TBI management.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70123","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:35:17Z","timestamp":1783154117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>ROS<\/scp>\n                    \u2010Responsive Quercetin Nanoparticles Improve the Prognosis of Traumatic Brain Injury by Inhibiting Aberrant Nrf2\u2010Keap1 Signaling Pathway Activation"],"prefix":"10.1002","volume":"114","author":[{"given":"YiFan","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Pathology Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou Jiangsu People's Republic of China"},{"name":"Dalian Medical University  Dalian Liaoning People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Pathology Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuihuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou Jiangsu People's Republic of China"},{"name":"Dalian Medical University  Dalian Liaoning People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Suqian Hospital Affiliated to Xuzhou Medical University  Suqian Jiangsu People's Republic of 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