{
  "abstract": "CD8⁺ T cell exhaustion driven by mitochondrial dysfunction remains a major barrier to effective cancer immunotherapy. Here, we report an in situ forming d-α-tocopheryl polyethylene glycol succinate (TPGS)-based hydrogel [multifunctional thermosensitive composite gel (MTC Gel)] that reinvigorates exhausted CD8⁺ T cells by preserving mitochondrial fitness through a two-pronged strategy. After intratumoral injection, MTC Gel rapidly undergoes gelation at physiological temperature and dissociates to generate a high local concentration of TPGS, which targets cancer cell mitochondria to trigger prodeath mitophagy. This process induces robust immunogenic cell death (ICD) and blocks tunneling nanotube-mediated mitochondrial hijacking. Meanwhile, NLG919-loaded hybrid nanoparticles released from MTC Gel synergistically restore mitochondrial biogenesis in CD8⁺ T cells suppressed by indoleamine 2,3-dioxygenase 1. Across multiple murine tumor models, MTC Gel reprograms T cell immunity by reducing CD8⁺ T cells exhaustion while enhancing effector and cytotoxic functions, thereby eliciting potent tumoricidal activity. These findings highlight this rationally designed hydrogel system as a clinically translatable platform for next-generation ICD-based cancer immunotherapies.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Key Laboratory for Molecular Engineering for Chiral Drugs, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China.",
    "Department of Pharmacy, Putuo People’s Hospital, School of Medicine, Tongji University, Shanghai 200060, P.R. China.",
    "Instrumental Analysis Centre, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.",
    "Rehabilitation Department, Yancheng No.1 People’s Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng 224000, P.R. China.",
    "Biomedical Polymers Laboratory, College of Chemistry Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, P.R. China.",
    "Shanghai Frontiers Science Center of Drug Target Identification and Delivery, Shanghai Jiao Tong University, Shanghai, P.R. China.",
    "School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yiming Qi",
      "orcid": "0000-0002-0530-6661"
    },
    {
      "affs": [
        1
      ],
      "name": "Jing Li",
      "orcid": "0009-0000-0571-6022"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyan Chen",
      "orcid": "0009-0006-8297-1258"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenming Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Haichao Zhu",
      "orcid": "0009-0004-4271-9918"
    },
    {
      "affs": [
        0
      ],
      "name": "Alice Shen Yi Shan",
      "orcid": "0009-0007-7977-4453"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuli Fu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jingwen Hou"
    },
    {
      "affs": [
        3
      ],
      "name": "Chaozhu Zheng"
    },
    {
      "affs": [
        4
      ],
      "name": "Qiongzhe Ren",
      "orcid": "0000-0002-0904-3627"
    },
    {
      "affs": [
        5
      ],
      "name": "Yu Qiao",
      "orcid": "0000-0001-5945-4734"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhu Jin",
      "orcid": "0000-0001-6619-7705"
    },
    {
      "affs": [
        6
      ],
      "name": "Feihu Wang",
      "orcid": "0000-0002-0358-967X"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengrong Guo",
      "orcid": "0000-0002-6897-2055"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1vc0a70xt0yj4.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.adz0039",
  "fulltext_url": "https://europepmc.org/articles/PMC13693686",
  "id": "1vc0a70xt0yj4",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.adz0039",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223340917",
  "pdf_url": "https://europepmc.org/articles/PMC13693686?pdf=render",
  "pmcid": "PMC13693686",
  "pmid": "42913016",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/1vc0a70xt0yj4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.adz0039",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.adz0039"
    },
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42913016",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42913016"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "An in situ forming immunomodulatory hydrogel reinvigorates exhausted CD8 ⁺ T cells via preserving their mitochondrial fitness",
  "title_text": "An in situ forming immunomodulatory hydrogel reinvigorates exhausted CD8 ⁺ T cells via preserving their mitochondrial fitness",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/1vc0a70xt0yj4",
  "venue": "Science Advances",
  "versions": []
}