Bimetallic modified titanium carbide nanoparticles loaded with transcription factor E3 ameliorate intervertebral disc degeneration by eliminating reactive oxygen species and promoting autophagic flux.

Intervertebral disc (IVD) degeneration (IVDD) is a major cause of lower back pain, characterized by oxidative stress accumulation and impaired autophagic flux leading to nucleus pulposus cell (NPC) degeneration. Transcription factor E3 (TFE3) is crucial in autophagy regulation. MXene, a nanomaterial known for its antioxidant capability, exhibits satisfactory therapeutic effects in various diseases. This study investigates the role of TFE3 and evaluates the therapeutic potential of Ti3C2 MXene-based nanocomposites in IVDD. The Ti3C2@PtAu@TFE3 nanocomposite was designed, with properties of anti-oxidation and pro-autophagic flux, alleviated extracellular matrix (ECM) degradation and senescence in NPCs. In a needle puncture-induced IVDD rat model, intra-disc injection of Ti3C2@PtAu@TFE3 alleviated structural deterioration and prevented ECM destruction. This study highlights the critical role of TFE3 in IVDD pathogenesis and demonstrates the potential application of Ti3C2@PtAu@TFE3 against IVDD.