title: Urocanic acid-modified chitosan nanoparticles can confer anti-inflammatory effect by delivering CD98 siRNA to macrophages.
abstract: CD98 plays an important role in the development and progression of inflammation. Here, CD98 siRNA (siCD98) was complexed with urocanic acid-modified chitosan (UAC) to form nanoparticles (NPs), which were transfected into Raw 264.7 macrophages in an effort to convey anti-inflammatory effects. Characterization showed that the generated NPs had a desirable particle size (156.0-247.1nm), a slightly positive zeta potential (15.8-17.5mV), and no apparent cytotoxicity against Raw 264.7 macrophages and colon-26 cells compared to control NPs fabricated by Oligofectamine (OF) and siRNA. Cellular uptake experiments demonstrated that macrophages exhibited a time-dependent accumulation profile of UAC/siRNA NPs. Further in vitro gene silencing experiments revealed that UAC/siCD98 NPs with a weight ratio of 60:1 yielded the most efficient knockdowns of CD98 and the pro-inflammatory cytokine, TNF-α. Indeed, the RNAi efficiency obtained with our NPs was even higher than that of the positive control OF/siCD98 NPs. These results suggest that UAC/siCD98 NPs might be a safe, efficient and promising candidate for the treatment of inflammatory disease.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing 400715, PR China; Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta 30302, USA. Electronic address: bxiao@gsu.edu.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing 400715, PR China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ma
authors.affiliation: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, 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: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, 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: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D027261:Fusion Regulatory Protein-1 / Q000235:genetics*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014560:Urocanic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000893:Anti-Inflammatory Agents; D027261:Fusion Regulatory Protein-1; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D048271:Chitosan; D014560:Urocanic Acid
keywords: Anti-inflammation; CD98 siRNA; Chitosan; Macrophage; Nanoparticle; Urocanic acid