{
  "abstract": "Alzheimer's disease (AD), characterized by amyloid (Aβ) deposition in neurons, is the most serious neurodegenerative disorder, but lacks effective therapeutic drugs in the clinic. Impaired neuronal lysosomal function drives the pathological accumulation of intracellular Aβ. Targeted rehabilitation of lysosomal dysfunction may offer a potential strategy to restore neuronal homeostasis and mitigate AD progression. In this study, we developed a brain-targeted smart lipid nanoparticle (A-PSL@7BIO) to repair lysosomal membrane damage and restore impaired acidification in the brain for AD therapy. The system was composed of Angiopep-2 peptide-conjugated lipid nanoparticles, which were loaded with a Glycogen synthase kinase-3β (GSK-3β) inhibitor 7-bromoindirubin-3'-oxime (7BIO) and incorporated with dipalmitoyl-phosphatidylserine (DPPS) and a reactive oxygen species (ROS) responsive phospholipid. Through Angiopep-2-mediated blood-brain barrier (BBB) transcytosis, the smart lipid nanoparticles could enhance brain biodistribution with subsequent neuronal internalization. Pathologically elevated intracellular ROS levels in AD could induce stimulus-responsive payload release, wherein 7BIO selectively inhibited aberrant GSK-3β hyperphosphorylation to restore the physiological acidic lysosomal environment and DPPS structurally repaired compromised lysosomal membranes, synergistically addressing dual aspects of lysosomal pathology. This smart lipid nanoparticles synergistically restored physiological lysosomal homeostasis, reversed neuronal dysfunction, and ameliorated cognitive deficits in AD models, indicating that A-PSL@7BIO could be used as a potential nanomedicine for AD therapy.",
  "abstract_shown": true,
  "affiliations": [
    "The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University; Pharmacy School of Nanjing Medical University, Nanjing 211166, China.",
    "Jiangsu Province Innovation Center for Brain-Inspired Intelligence Technology, Nanjing 210000, China.",
    "Department of Pharmacy, The Affiliated Jiangyin Clinical College of Xuzhou Medical University, Jiangyin 214400, China.",
    "School of Basic Medical Sciences Nanjing Medical University, Nanjing 211166, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiaqing Yin"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Lv"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wei Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhenwei Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Fei Zhu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongli Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shengnan Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiang Cao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Linfeng Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kefan Song"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yue Gong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiangna Xu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuqin Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhiyuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangming Fang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongliang Xin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b4d7c79t55368.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.06.036",
  "fulltext_url": "https://europepmc.org/articles/PMC13712284",
  "id": "b4d7c79t55368",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948702",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ]
  ],
  "openalex": "W7165546642",
  "pdf_url": "https://europepmc.org/articles/PMC13712284?pdf=render",
  "pmcid": "PMC13712284",
  "pmid": "42948702",
  "published": "2026-06-22",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/b4d7c79t55368.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948702",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948702"
    },
    {
      "first_seen": "2026-10-31T12:22:54Z",
      "native_id": "PMC13712284",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.06.036"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2502|Nanoparticle-Based Drug Delivery",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Lysosomal membrane damage repair and acidification impairment restoration triggered by smart lipid nanoparticles for Alzheimer's disease treatment.",
  "title_text": "Lysosomal membrane damage repair and acidification impairment restoration triggered by smart lipid nanoparticles for Alzheimer's disease treatment.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:54Z",
  "url": "https://research.draconitic.com/paper/b4d7c79t55368",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}