title: Macrophage-mediated nanoparticle delivery to the periodontal lesions in established murine model via Pg-LPS induction.
abstract: We established a murine periodontitis model by local injection of lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS) into the gingival sulcus of mandibular left incisor four times with 48-h interval. The histological examination of the periodontal tissues demonstrated that significant loss of periodontal bone and ligaments was observed in the lesion side with abundant inflammatory cell infiltration. Two days after the last injection, Cy5-labelled siRNA/chitosan particles were injected intraperitoneally (ip). The chitosan/siRNA particles were taken up by peritoneal macrophages, which subsequently migrated to the inflamed gingival area evaluated by in vivo imaging. The localization of macrophages in the inflamed region was further confirmed by immunofluorescent staining. The present report demonstrates that intragingival injection of Pg-LPS can be used to create an experimental model of periodontal inflammation in mice and that recruitment of macrophages with chitosan/siRNA nanoparticles to the inflamed area opens the possibility of an RNAi-based therapeutic approach using chitosan as a carrier in periodontitis.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi-an, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.affiliation: Department of Dentistry, Health, Aarhus University, Aarhus C, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Løvschall
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prothodontics, School of Stomatology, The Fourth Military Medical University, Xi-an, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Gitte K
authors.initials: GK
authors.lastname: Nielsen
authors.affiliation: Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
authors.forename: Chuanxu
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi-an, China.
authors.forename: Qintao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.affiliation: Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D016301:Alveolar Bone Loss / Q000473:pathology; D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010518:Periodontitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016966:Porphyromonas gingivalis; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D000067492:RNAi Therapeutics / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D002232:Carbocyanines; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C085321:cyanine dye 5; D048271:Chitosan
keywords: chitosan/siRNA nanoparticle; macrophages; mouse model; periodontitis