Nanoparticles Carrying NF-κB p65-Specific siRNA Alleviate Colitis in Mice by Attenuating NF-κB-Related Protein Expression and Pro-Inflammatory Cellular Mediator Secretion

Abstract

Ulcerative colitis is a disease that causes inflammation and ulcers in the colon and which is typically recurrent, and NF-κB proteins are important players during disease progression. Here, we assess the impact of silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against NF-κB p65 on a murine model of colitis. To this end, nanoparticles were injected intravenously (2.0 mg siRNA/kg body weight) into mice after colitis induction with dextran sulfate sodium or healthy ones. The disease activity index, the histopathological impact on the colon, the protein expression of several NF-κB-associated players, and the mediator secretion (colon tissue, blood) were analyzed. We found that the nanoparticles effectively alleviated the clinical and histopathological features of colitis. They further suppressed the expression of NF-κB proteins (e.g., p65, p50, p52, p100, etc.) in the colon. They finally attenuated the local (colon) or systemic (blood) pro-inflammatory mediator secretion (e.g., TNF-α, IFN-β, MCP-1, interleukins, etc.) as well as the leucocyte load of the spleen and mesenteric lymph nodes. The nanoparticle biodistribution in diseased animals was seen to pinpoint organs containing lymphoid entities (appendix, intestine, lung, etc.). Taken together, the nanoparticle-related silencing of p65 NF-κB protein expression could well be used for the treatment of ulcerative colitis in the future.

Keywords

• NF-κB p65
• gene silencing
• DSS-induced colitis
• inflammatory bowel disease
• ulcerative colitis
• calcium phosphate