title: Targeting intestinal inflammation with CD98 siRNA/PEI-loaded nanoparticles.
abstract: Intestinal CD98 expression plays a crucial role in controlling homeostatic and innate immune responses in the gut. Modulation of CD98 expression in intestinal cells therefore represents a promising therapeutic strategy for the treatment and prevention of inflammatory intestinal diseases, such as inflammatory bowel disease. Here, the advantages of nanoparticles (NPs) are used, including their ability to easily pass through physiological barriers and evade phagocytosis, high loading concentration, rapid kinetics of mixing and resistance to degradation. Using physical chemistry characterizations techniques, CD98 siRNA/polyethyleneimine (PEI)-loaded NPs was characterized (diameter of ~480 nm and a zeta potential of -5.26 mV). Interestingly, CD98 siRNA can be electrostatically complexed by PEI and thus protected from RNase. In addition, CD98 siRNA/PEI-loaded NPs are nontoxic and biocompatible with intestinal cells. Oral administration of CD98/PEI-loaded NPs encapsulated in a hydrogel reduced CD98 expression in mouse colonic tissues and decreased dextran sodium sulfate-induced colitis in a mouse model. Finally, flow cytometry showed that CD98 was effectively downregulated in the intestinal epithelial cells and intestinal macrophages of treated mice. Finally, the results collectively demonstrated the therapeutic effect of "hierarchical nano-micro particles" with colon-homing capabilities and the ability to directly release "molecularly specific" CD98 siRNA in colonic cells, thereby decreasing colitis.
authors.affiliation: Department of Chemistry and Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Laroui
authors.affiliation: Department of Pathology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Duke
authors.initials: D
authors.lastname: Geem
authors.affiliation: Department of Chemistry and Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Chemistry and Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Department of Chemistry and Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Rakhya
authors.affiliation: Department of Pathology, School of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Denning
authors.affiliation: 1] Department of Chemistry and Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA [2] Veterans Affairs Medical Center, Decatur, Georgia, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D027261:Fusion Regulatory Protein-1 / Q000737:chemistry* / Q000235:genetics; D018014:Gene Transfer Techniques; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics
chemical_list: D027261:Fusion Regulatory Protein-1; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D016264:Dextran Sulfate
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