TGF-β 1 -siRNA delivery with nanoparticles inhibits peritoneal fibrosis

Abstract

Gene therapies may be promising for the treatment of peritoneal fibrosis (PF) in subjects undergoing peritoneal dialysis (PD). However, a method of delivery of treatment genes to the peritoneum is lacking. We attempted to develop an in vivo small interfering RNA (siRNA) delivery system with liposome-based nanoparticles (NPs) to the peritoneum to inhibit PF. Transforming growth factor (TGF)-β 1 -siRNAs encapsulated in NPs (TGF-β 1 -siRNAs-NPs) dissolved in PD fluid were injected into the peritoneum of mice with PF three times a week for 2 weeks. TGF-β 1 -siRNAs-NPs knocked down TGF-β 1 expression significantly in the peritoneum and inhibited peritoneal thickening with fibrous changes. TGF-β 1 -siRNAs-NPs also inhibited the increase of expression of -smooth muscle actin-positive myofibroblasts. These results suggest that the TGF-β 1 -siRNA delivery system with NPs described here could be an effective therapeutic option for PF in subjects undergoing PD.