title: Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation.
abstract: Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation bothin vitroandin vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.; Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Moon Kwon
authors.initials: MK
authors.lastname: Han
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001688:Biological Products / Q000008:administration & dosage*; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000502:physiology; D003474:Curcumin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects; D027261:Fusion Regulatory Protein-1 / Q000037:antagonists & inhibitors; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000502:physiology*; D019344:Lactic Acid / Q000008:administration & dosage; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D004337:Drug Carriers; D027261:Fusion Regulatory Protein-1; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid; D003474:Curcumin
keywords: anti-inflammation; combination therapy; mucosal protection; oral administration; targeted nanoparticle; ulcerative colitis.