PLGA microspheres loaded with si-circETS1 as a therapeutic strategy to delay intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is one of the leading causes of chronic low back pain and functional impairment, severely affecting the quality of life of patients. In recent years, circular RNA (circRNA), has gained attention for its critical role in cellular function regulation, especially its potential therapeutic effects in IDD. This study aims to elucidate the function of circETS1 in nucleus pulposus cells (NPCs) and develop a novel targeted therapeutic strategy. CircETS1, which was abnormally highly expressed in degenerated nucleus pulposus tissue, was identified through circRNA sequencing (circRNA-seq). The circular nature of circETS1 was confirmed by Sanger sequencing, RNase R digestion, and fluorescence in situ hybridization (FISH). Primary human NPCs were cultured, and the effects of regulating circETS1 on cell proliferation, apoptosis, and extracellular matrix metabolism were studied using reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, flow cytometry, and immunofluorescence. Polylactic-co-glycolic acid (PLGA) microspheres (MS) loaded with si-circETS1 were prepared, and their therapeutic effects were evaluated. PLGA MS loaded with si-circETS1 effectively delivered si-circETS1 to nucleus pulposus tissue in both in vitro and in vivo experiments, significantly downregulating circETS1 expression, reducing inflammation, promoting extracellular matrix synthesis and repair, and ultimately delaying the progression of IDD. Consequently, PLGA MS loaded with si-circETS1 present an innovative and promising therapeutic strategy for IDD, demonstrating strong potential for clinical application.