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A Single-Cell-Inspired Self-Enrichment Therapeutic Strategy Delays Intervertebral Disc Degeneration by Inhibiting

Hao Zhou1, Hao Ning2, Qianqi Liu1

  • 1Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, P. R. China.

Advanced Materials (Deerfield Beach, Fla.)
|November 5, 2025
PubMed

Insights

Intervertebral disc degeneration (IVDD) is a major cause of back pain. Researchers developed a novel nanocarrier to deliver drugs effectively to degenerated discs, significantly slowing IVDD progression.

Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Nanotechnology

Background:

  • Intervertebral disc degeneration (IVDD) is a leading cause of spinal surgery, with current treatments unable to halt or reverse its progression due to poor drug delivery and limited mechanistic understanding.
  • Degenerative tissues exhibit a fibrotic barrier hindering therapeutic access, and nucleus pulposus cells undergo pyroptosis driven by STING-mediated inflammation.
  • A comprehensive cellular atlas is needed to understand IVDD mechanisms and develop targeted therapies.

Purpose of the Study:

  • To construct a cellular atlas for IVDD by integrating single-cell transcriptomics and clinical data.
  • To identify key mechanisms driving IVDD, including fibrotic barriers and pyroptosis.
  • To develop and validate a novel nanocarrier system for targeted drug delivery to degenerated intervertebral discs.

Main Methods:

  • Single-cell transcriptomics and clinical validation were used to create a cellular atlas of IVDD.
  • A self-enriching nanocarrier (Motor@TA-siRNA) was designed to overcome fibrotic barriers via bubble propulsion.
  • Small interfering ribonucleic acid (siRNA) was incorporated for targeted delivery to the STING pathway, inhibiting inflammation and pyroptosis.

Main Results:

  • The study identified a fibrotic barrier in degenerative discs impeding drug delivery.
  • Pyroptosis in nucleus pulposus cells, mediated by STING, was confirmed as a key inflammatory mechanism.
  • The Motor@TA-siRNA nanocarrier demonstrated selective penetration into degenerated tissues and effectively inhibited STING-mediated inflammation and pyroptosis.
  • In vitro and in vivo studies confirmed the nanocarrier's biocompatibility and efficacy in delaying IVDD progression.

Conclusions:

  • A synergistic strategy combining mechanistic insight and nanocarrier design offers a promising approach for IVDD therapy.
  • The developed nanocarrier system effectively targets the STING pathway, mitigating inflammation and pyroptosis.
  • This study provides a foundation for personalized IVDD treatment by addressing key pathological features and improving drug delivery.
Keywords:
intervertebral disc degenerationpyroptosisself‐enriching nanocarriersiRNA deliverysingle‐cell sequencing

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