title: Lipidoid Nanoparticles for siRNA Delivery to the Intestinal Epithelium: In Vitro Investigations in a Caco-2 Model.
abstract: Short interfering ribonucleic acid (siRNA) therapeutics show promise for the treatment of intestinal diseases by specifically suppressing the expression of disease relevant proteins. Recently, a class of lipid-like materials termed "lipidoids" have been shown to potently deliver siRNA to the liver and immune cells. Here, we seek to establish the utility of lipidoid nanoparticles (LNPs) in the context of siRNA delivery to the intestinal epithelium. Initial studies demonstrated that the siRNA-loaded LNPs mediated potent, dose dependent, and durable gene silencing in Caco-2 intestinal epithelial cells, with a single 10 nM dose depressing GAPDH mRNA expression for one week. Transfection with siRNA-loaded LNPs did not induce significant cytotoxicity in Caco-2 cells or alter intestinal barrier function. Protein silencing was confirmed by Western blotting, with the lowest levels of GAPDH protein expression observed five days post-transfection. Together, these data underscore the potential of LNPs for the treatment of intestinal disorders.
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Ball
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Knapp
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Whitehead
mesh_terms: D018938:Caco-2 Cells; D020868:Gene Silencing; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection / Q000379:methods*
chemical_list: D034741:RNA, Small Interfering; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)