Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice

• Published in: Inflammation research Vol. 63; no. 2; pp. 139 - 147
• Main Authors: Maehara, Ami, Nishida, Keiichiro, Furutani, Masumi, Matsumoto, Emi, Ohtsuka, Aiji, Ninomiya, Yoshifumi, Oohashi, Toshitaka
• Format: Journal Article
• Language: English
• Published: Basel Springer Basel 01-02-2014; Springer Nature B.V
• Subjects: Allergology; Animals; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Biomedical and Life Sciences; Biomedicine; Dermatology; E-Selectin - metabolism; Foot Joints - metabolism; Foot Joints - pathology; Foot Joints - ultrastructure; Gold Colloid - administration & dosage; Immunology; Knee Joint - metabolism; Knee Joint - pathology; Knee Joint - ultrastructure; Liposomes; Lysosomes - metabolism; Lysosomes - ultrastructure; Macrophages - metabolism; Macrophages - ultrastructure; Mice; Mice, Inbred DBA; Microscopy - methods; Microscopy, Electron, Transmission; Neurology; Oligosaccharides - metabolism; Original Research Paper; Pharmacology/Toxicology; Rheumatology; Active targeting-liposome; Arthritis; Drug delivery; Colloidal gold; Electron microscopy
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-013-0682-4

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.