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Tetrahedral Framework Nucleic Acid-Based Cepharanthine Attenuates TMJOA via cGAS-STING-NF-κB Pathway Modulation and

Shibo Liu1, Hanghang Liu1,2, Qiheng Yang1

  • 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.

ACS Applied Materials & Interfaces
|January 7, 2026
PubMed
Summary

A novel nanoplatform (tFNA@Cep) effectively treats temporomandibular joint osteoarthritis (TMJOA) by reducing inflammation and promoting cartilage repair. This nanotherapeutic offers a promising strategy for TMJOA and other joint disorders.

Keywords:
cGAS−STING pathwaycepharanthinemacrophage reprogrammingtemporomandibular joint osteoarthritistetrahedral framework nucleic acid

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Osteoarthritis Research

Background:

  • Temporomandibular joint osteoarthritis (TMJOA) is a degenerative condition with limited effective treatments.
  • Characterized by cartilage degradation, bone remodeling, and inflammation, TMJOA significantly impacts patient quality of life.

Purpose of the Study:

  • To develop and evaluate a novel cepharanthine-loaded tetrahedral framework nucleic acid nanoplatform (tFNA@Cep) for TMJOA treatment.
  • To assess the physicochemical properties, biological performance, and therapeutic efficacy of tFNA@Cep in a murine TMJOA model.

Main Methods:

  • Fabrication and characterization of the tFNA@Cep nanoplatform.
  • Induction of TMJOA in a murine model using unilateral anterior crossbite.
  • Evaluation of therapeutic effects on cartilage, subchondral bone, and inflammatory pathways.

Main Results:

  • tFNA@Cep demonstrated excellent stability, cellular uptake, and structural integrity.
  • Treatment significantly improved cartilage thickness and subchondral bone, restoring Col II and RUNX2 expression.
  • tFNA@Cep modulated macrophage polarization to an anti-inflammatory M2 phenotype, suppressed the cGAS-STING-NFκB pathway, and reduced ROS production.

Conclusions:

  • tFNA@Cep acts as a multifunctional nanotherapeutic agent for TMJOA.
  • It effectively integrates drug delivery, inflammation resolution, and osteochondral repair.
  • This nanoplatform presents a promising therapeutic strategy for TMJOA and related joint diseases.