Caffeic acid borate functionalized linear polyglycidol for targeted siRNA delivery in the treatment of primary biliary cholangitis.

Interfering with protein arginine methyltransferase 5 (PRMT5) gene expression with siRNA targeting is a promising strategy for precision primary biliary cholangitis (PBC) therapy, yet achieving effective and specific delivery of therapeutic agents to the liver remains challenging. In this study, we develop a caffeic acid borate derived linear polyglycidol polymer micelle CAPG, which can efficiently deliver siRNA to liver. The degradation of borate and hydrazone bonds in the high-ROS and acidic environment of inflammatory cells triggers micelle disintegration, facilitating siRNA release. Comprehensive in vivo experiments demonstrate that siRNA1@CAPG can significantly reduce the concentration of liver inflammation-related biomarkers and pro-inflammatory factors and notably increase superoxide dismutase (SOD) levels in mice, outperforming free siRNA1 in suppressing PRMT5 expression. Therefore, our study offers valuable reference for the treatment of primary biliary cholangitis.