{
  "abstract": "Intervertebral disc degeneration is a major cause of chronic low back pain, but effective disease-modifying therapies remain unavailable. Sustained and localized RNA interference (RNAi) offers a promising therapeutic approach; however, its application to the disc is limited by poor local retention and delivery-related toxicity. Here, we developed a release-controlled RNAi platform using biodegradable cationized gelatin nanospheres (cGNS) to deliver small interfering RNA (siRNA) targeting Rptor, which encodes RPTOR, a key component of the mechanistic target of rapamycin complex 1 (mTORC1). cGNS enabled longer-term intracellular siRNA retention with lower toxicity than conventional lipofection, leading to a prolonged decrease in RPTOR expression, autophagy activation, and suppressed apoptosis, senescence, and matrix breakdown. Intradiscal delivery of Rptor siRNA with cGNS preserved radiographic tissue morphology, maintained histological matrix integrity, and reduced cellular degeneration markers. Benefits were observed in both preventive and post-traumatic settings. cGNS-mediated controlled release of RNAi against Rptor is a durable therapeutic strategy for degenerative disc disease through mTORC1 inhibition.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.",
    "Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.",
    "Department of Orthopedic Surgery, Iwate Medical University School of Medicine, Yahaba, Japan.",
    "Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
    "Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoshiaki Hiranaka"
    },
    {
      "affs": [
        0
      ],
      "name": "Takashi Yurube"
    },
    {
      "affs": [
        0
      ],
      "name": "Naotoshi Kumagai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshiki Takeoka"
    },
    {
      "affs": [
        0
      ],
      "name": "Yutaro Kanda"
    },
    {
      "affs": [
        0
      ],
      "name": "Kohei Kuroshima"
    },
    {
      "affs": [
        0
      ],
      "name": "Masahiko Furuya"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Nakagawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Takahiro Kitano"
    },
    {
      "affs": [
        0
      ],
      "name": "Akihiro Miyajima"
    },
    {
      "affs": [
        1
      ],
      "name": "Taichi Washisaka"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kenichiro Kakutani"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryosuke Kuroda"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yasuhiko Tabata"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/19ep24e5rkasd.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bioactmat.2026.09.033",
  "fulltext_url": "https://europepmc.org/articles/PMC13678022",
  "id": "19ep24e5rkasd",
  "issns": [
    "2452-199X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898649",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7221463033",
  "pdf_url": "https://europepmc.org/articles/PMC13678022?pdf=render",
  "pmcid": "PMC13678022",
  "pmid": "42898649",
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/19ep24e5rkasd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42898649",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898649"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Spine and Intervertebral Disc Pathology",
      "subfield": "general"
    }
  ],
  "title": "Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.",
  "title_text": "Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/19ep24e5rkasd",
  "venue": "Bioactive materials",
  "versions": []
}