title: Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice.
abstract: OBJECTIVE
  We have previously demonstrated the efficient and time-dependent transvascular localization of Sialyl Lewis X (SLX)-liposomes to inflammatory sites, but the final target of the SLX-liposomes remained uncertain. The aim of this study was to identify the target cells of the liposomes within the inflamed joints of collagen antibody-induced arthritis (CAIA) model mice.
  
  
  METHODS
  SLX-liposomes and unlabeled liposomes encapsulating high-density colloidal gold were administered intravenously into the caudal vein of CAIA mice on day 5 after induction of arthritis when the inflammatory score was maximal (n = 6 per group). Six hours or 24 h after liposome administration, animals were euthanized and hind limbs and ankles were excised without perfusion. After fixation, synovial tissues were examined by light microscopy after silver enhancement of colloidal gold or by transmission electron microscopy.
  
  
  RESULTS
  Silver-enhanced signals were detected within the cells around E-selectin-positive blood vessels in the synovium of the SLX-liposome group. These cells were positive for the macrophage/monocyte marker F4/80 or neutrophil marker Ly-6G. Transmission electron microscopy detected the colloidal gold signals together with liposome-like structures within the phagosomes of synovial macrophages. Transmission electron microscopy and energy dispersive X-ray spectrometry could determine gold elements in the lysosomes of synovial macrophages.
  
  
  CONCLUSIONS
  The results of the current study demonstrate that SLX-liposomes primarily targeting E-selectin in activated endothelial cells could potentially deliver their contents into inflammatory cells around synovial blood vessels in arthritic joints.
authors.affiliation: Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Maehara
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Masumi
authors.initials: M
authors.lastname: Furutani
authors.forename: Emi
authors.initials: E
authors.lastname: Matsumoto
authors.forename: Aiji
authors.initials: A
authors.lastname: Ohtsuka
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Oohashi
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D019040:E-Selectin / Q000378:metabolism*; D033023:Foot Joints / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017979:Gold Colloid / Q000008:administration & dosage*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008081:Liposomes; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008811:Mice, Inbred DBA; D008853:Microscopy / Q000379:methods; D046529:Microscopy, Electron, Transmission; D009844:Oligosaccharides / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
chemical_list: D019040:E-Selectin; D017979:Gold Colloid; D008081:Liposomes; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen