{
  "abstract": "Intervertebral disc degeneration (IVDD) is fundamentally driven by a self-perpetuating pathological loop involving metabolic derangement, oxidative stress, and enzymatic hyper-activity. Conventional mono-therapies often fall short of reversing this complex microenvironmental collapse. Here, we developed a smart nano-glycosphere (siMMP13/2-DG NPs) designed for dual-track intervention to restore disc homeostasis. This responsive platform utilized a 2-deoxy-D-glucose (2-DG) shell crosslinked via reactive oxygen-sensitive phenylboronic acid moieties, enabling the simultaneous suppression of pathological glycolysis and the neutralization of oxidative stress. Concomitantly, the precise delivery of siMMP13 effectively silenced major catabolic enzymes, thereby arresting extracellular matrix degradation. Our findings demonstrated that this combinatorial approach effectively interrupted the lactate-driven inflammatory cascade, shifting the microenvironment from a hostile catabolic state toward a pro-regenerative metabolic balance. In the lumbar disc degeneration model, the siMMP13/2-DG NPs significantly preserved structural integrity and alleviated discogenic pain by dampening neuro-inflammatory signaling. By integrating metabolic reprogramming with targeted gene silencing, this study establishes a versatile therapeutic paradigm for the precision management of IVDD and offers broader insights into the treatment of other microenvironment-mediated musculoskeletal disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China.",
    "Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.",
    "Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.",
    "Pain Research Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.",
    "Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. zhzhaom@mail.sysu.edu.cn.",
    "Pain Research Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. zhzhaom@mail.sysu.edu.cn.",
    "Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China. liuhm@sustech.edu.cn.",
    "Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China. wudc@sustech.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lei Zhao",
      "orcid": "0009-0004-0743-4095"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wenzheng Ma"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Wantao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinghao Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingkang Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xue Wei"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Zhaomin Zheng"
    },
    {
      "affs": [
        6
      ],
      "name": "Hongmei Liu"
    },
    {
      "affs": [
        7
      ],
      "name": "Decheng Wu",
      "orcid": "0000-0002-5276-8607"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fapcmww5m84xx.bib",
  "cited_by": 0,
  "doi": "10.1186/s12951-026-04830-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13678946",
  "id": "fapcmww5m84xx",
  "issns": [
    "1477-3155"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894235",
  "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": [
    [
      "lcc",
      "R855-855.5"
    ],
    [
      "lcc",
      "TP248.13-248.65"
    ],
    [
      "openalex",
      "2734|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7170079405",
  "pdf_url": "https://europepmc.org/articles/PMC13678946?pdf=render",
  "pmcid": "PMC13678946",
  "pmid": "42894235",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/fapcmww5m84xx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:42Z",
      "native_id": "MED:42894235",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894235"
    },
    {
      "first_seen": "2026-10-30T13:46:19Z",
      "native_id": "31f48843dda64235a9731dbb3f7c6f45",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s12951-026-04830-3"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "lcc:TP248.13-248.65",
      "subfield": "systems-synthetic"
    },
    {
      "field": "medicine",
      "origin": "lcc:R855-855.5",
      "subfield": "general"
    }
  ],
  "title": "Pathological microenvironment-responsive nano-glycospheres restore disc homeostasis by combinatorial metabolic and genetic regulation.",
  "title_text": "Pathological microenvironment-responsive nano-glycospheres restore disc homeostasis by combinatorial metabolic and genetic regulation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:19Z",
  "url": "https://research.draconitic.com/paper/fapcmww5m84xx",
  "venue": "Journal of nanobiotechnology",
  "versions": []
}