Modulation of Intestinal Inflammatory Processes by Specific Knockdown of Cytokines with siRNA-functionalized Calcium Phosphate Nanoparticles

Inflammatory bowel disease is a group of chronic inflammatory conditions of the small and large intestine. The available therapies are only symptomatic and currently used drugs often lead to severe side effects or show no clinical improvements in some patients; therefore the development of new medications is reasonable. The interference of cytokine signaling mediated by siRNA might be a promising new therapeutic approach. In this project we analyze the potency of biodegradable calcium phosphate nanoparticles for the specific delivery of siRNA to the large intestine. We showed that the rectal application of these nanoparticles functionalized with siRNA directed against TNF-α, KC or IP-10 to mice suffering from DSS-induced colitis led to decreased expression with reduced protein levels of the target genes in colonic biopsies and mesenteric lymph nodes. These findings were accompanied by an amelioration of intestinal inflammation. In conclusion, these experiments imply that the specific and local modulation of the inflammatory response by a nanoparticle-based siRNA delivery system could be a promising approach for the treatment of intestinal inflammation.