Bioactive materialsOct 20, 2026

Controlled RNA delivery using charged gelatin nanoparticles may protect against spinal disc degeneration by targeting mTORC1

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 21, 2026

Abstract

Sustained and localized RNA interference using biodegradable cationized gelatin nanospheres may provide a durable therapeutic strategy for intervertebral disc degeneration.

Intradiscal delivery of siRNA targeting Rptor resulted in a prolonged decrease in RPTOR expression.
Lower toxicity was observed with cGNS compared to conventional lipofection, allowing for longer-term intracellular siRNA retention.
Activation of autophagy was noted, alongside suppression of apoptosis, senescence, and matrix breakdown.
Radiographic tissue morphology was preserved, and histological matrix integrity was maintained after treatment.
Cellular degeneration markers were reduced, indicating potential benefits in both preventive and post-traumatic settings.

Simplified

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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Controlled RNA delivery using charged gelatin nanoparticles may protect against spinal disc degeneration by targeting mTORC1

Abstract

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