{
  "abstract": "Ischemic stroke (IS) causes severe neurological deficits closely linked to microglial overactivation after ischemia/reperfusion (I/R) injury, a process governed by mitochondrial homeostasis. However, restoring microglial mitochondrial function across the blood–brain barrier (BBB) remains challenging. Here, we report a sequentially targeted nanosystem, M-BPM@TGPB, for I/R injury therapy. It comprises a triphenylphosphonium (TPP)-modified, gadolinium-doped Prussian blue core and a mannose-modified BV2–platelet hybrid membrane shell. This design integrates mannose for BBB penetration, platelet membrane for lesion targeting, BV2 membrane for microglial uptake, and TPP for mitochondrial localization, enabling precise vascular-to-subcellular delivery. In vitro, the nanosystem crossed the BBB, localized to BV2 mitochondria, scavenged reactive oxygen species (ROS), restored mitochondrial function, and inhibited inflammation. In a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R), the intravenously administered nanosystem accumulated in microglial mitochondria, scavenged mitochondrial ROS (mtROS), restored mitochondrial homeostasis, promoted M1-to-M2 polarization, suppressed neuroinflammation, reduced neuronal apoptosis, and promoted angiogenesis, thereby reducing infarct volume from 36.61% to 10.57% and the modified neurological severity score (mNSS) from 14 to 2.5. It also exhibited favorable biocompatibility and enhanced magnetic resonance imaging (MRI) contrast. Critically, rather than broadly scavenging ROS, this strategy specifically restores microglial mitochondrial function, shifting the therapeutic focus from general antioxidant approaches to organelle-specific intervention. This work may offer a promising design paradigm for nanotherapies targeting central nervous system disorders in which mitochondrial dysfunction and neuroinflammation are core pathological drivers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, Jiujiang City Key Laboratory of Cell Therapy/Human Genetic Resources Innovation Center, The First People's Hospital of Jiujiang City, Jiujiang, 332000, China",
    "Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China",
    "Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China",
    "Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China",
    "College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, 430065, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Qing Chen"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jin Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Hui Shu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaoxing Xiong"
    },
    {
      "affs": [
        2
      ],
      "name": "Lijuan Gu"
    },
    {
      "affs": [
        1
      ],
      "name": "Jian Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Youjia Tang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f8f10s3dq7n0s.bib",
  "cited_by": 0,
  "doi": "10.1016/j.mtbio.2026.103786",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733558/",
  "id": "f8f10s3dq7n0s",
  "issns": [
    "2590-0064"
  ],
  "landing_url": "https://doi.org/10.1016/j.mtbio.2026.103786",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Full Length Article"
    ],
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ]
  ],
  "openalex": "W7223986055",
  "pdf_url": null,
  "pmcid": "PMC13733558",
  "pmid": "42985190",
  "published": "2026-10-27",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/f8f10s3dq7n0s.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:18Z",
      "native_id": "PMC13733558",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.mtbio.2026.103786"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2502|Nanoparticle-Based Drug Delivery",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Sequential blood-brain barrier-penetrating and microglial-mitochondria-targeting nanosystem for ischemic stroke therapy",
  "title_text": "Sequential blood-brain barrier-penetrating and microglial-mitochondria-targeting nanosystem for ischemic stroke therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:18Z",
  "url": "https://research.draconitic.com/paper/f8f10s3dq7n0s",
  "venue": "Materials Today Bio",
  "versions": []
}