Microfluidic Synthesis of miR-200c-3p Lipid Nanoparticles: Targeting ZEB2 to Alleviate Chondrocyte Damage in Osteoarthritis

作者：Dong Zheng, Tong Chen, Kaiyuan Yang, Guangrong Yin, Yang Chen, Jianchao Gui, Chao Xu, Songwei Lv · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s491711 · 被引用次数：5 · 研究领域：Osteoarthritis Treatment and Mechanisms、MicroRNA in disease regulation、3D Printing in Biomedical Research

Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration. Chondrocyte inflammation, apoptosis, and extracellular matrix degradation accelerated OA progression. MicroRNA (miRNA) has the potential to be a therapeutic method for osteoarthritis. However, it is difficult to penetrate the cell to exercise its biological function, and its extracellular effect is unclear. Methods: lipo-AgPEI-miR-200c-3p was created by combining miR-200c-3p with silver nitrate polyvinylimine nanoparticles on a microfluidic device. The drug release curve, stability, temperature sensitivity, cytotoxicity, and the impact of lipo-AgPEI-miR-200c-3p on the expression of proteins linked to matrix disintegration, apoptosis, and inflammatory factors were all detected. Results: Results showed that the particle size of Lipo-AgPEI-miR-200c-3p was about 130 nm, the Zeta potential was lowered to 1.08±0.12 mV. Lipo-AgPEI-miR-200c-3p could increase cell viability, prevent cell apoptosis, and decrease the expression levels of TNF-α, IL-6, IL-1β, and MCP-1 in ADTC5 cells following LPS stimulation. MMP3, MMP13, and ADAMTS-4 expression was downregulated whereas collagen II expression was upregulated. The ZEB2 expression was greatly elevated following LPS stimulation and dramatically decreased following transfection of miR-200c-3p. Collagen II expression rose following transfection of si-ZEB2, whereas the expression levels of inflammatory factors, apoptosis-relate...