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Peer-reviewedCC BYBioactive materials

Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.

  • Yoshiaki Hiranaka1
  • Takashi Yurube1
  • Naotoshi Kumagai1
  • Yoshiki Takeoka1
  • Yutaro Kanda1
  • Kohei Kuroshima1
  • Masahiko Furuya1
  • Daisuke Nakagawa1
  • Takahiro Kitano1
  • Akihiro Miyajima1
  • Taichi Washisaka2
  • Kenichiro Kakutani1,3
2 more authors
  • Ryosuke Kuroda1
  • Yasuhiko Tabata4,5
5 affiliations
  1. 1Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
  2. 2Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  3. 3Department of Orthopedic Surgery, Iwate Medical University School of Medicine, Yahaba, Japan.
  4. 4Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. 5Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand.
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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.

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Cite

BibTeXRIS
BibTeX
@article{hiranaka2026cationized,
  title = {{Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.}},
  author = {Yoshiaki Hiranaka and Takashi Yurube and Naotoshi Kumagai and Yoshiki Takeoka and Yutaro Kanda and Kohei Kuroshima and Masahiko Furuya and Daisuke Nakagawa and Takahiro Kitano and Akihiro Miyajima and Taichi Washisaka and Kenichiro Kakutani and Ryosuke Kuroda and Yasuhiko Tabata},
  journal = {Bioactive materials},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bioactmat.2026.09.033},
  url = {https://europepmc.org/article/MED/42898649},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.
AU  - Yoshiaki Hiranaka
AU  - Takashi Yurube
AU  - Naotoshi Kumagai
AU  - Yoshiki Takeoka
AU  - Yutaro Kanda
AU  - Kohei Kuroshima
AU  - Masahiko Furuya
AU  - Daisuke Nakagawa
AU  - Takahiro Kitano
AU  - Akihiro Miyajima
AU  - Taichi Washisaka
AU  - Kenichiro Kakutani
AU  - Ryosuke Kuroda
AU  - Yasuhiko Tabata
PY  - 2026
DA  - 2026/10/11
JO  - Bioactive materials
DO  - 10.1016/j.bioactmat.2026.09.033
UR  - https://europepmc.org/article/MED/42898649
AB  - 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.
SN  - 2452-199X
ER  -