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

Ami Maehara, Keiichiro Nishida, Masumi Furutani, Emi Matsumoto, Aiji Ohtsuka, Yoshifumi Ninomiya, Toshitaka Oohashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 antibodyinduced 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.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalInflammation Research
Volume63
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Gold Colloid
Liposomes
Arthritis
Electrons
Inflammation
Light
Transmission Electron Microscopy
E-Selectin
Experimental Arthritis
Macrophages
Silver
Blood Vessels
Joints
X-Ray Emission Spectrometry
Phagosomes
Synovial Membrane
Lysosomes
Ankle
Gold
Monocytes

Keywords

  • Active targeting-liposome
  • Arthritis
  • Colloidal gold
  • Drug delivery
  • Electron microscopy

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

Cite this

Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice. / Maehara, Ami; Nishida, Keiichiro; Furutani, Masumi; Matsumoto, Emi; Ohtsuka, Aiji; Ninomiya, Yoshifumi; Oohashi, Toshitaka.

In: Inflammation Research, Vol. 63, No. 2, 2014, p. 139-147.

Research output: Contribution to journalArticle

@article{c811b9d778dd49049640f11ab51f1d35,
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 antibodyinduced 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.",
keywords = "Active targeting-liposome, Arthritis, Colloidal gold, Drug delivery, Electron microscopy",
author = "Ami Maehara and Keiichiro Nishida and Masumi Furutani and Emi Matsumoto and Aiji Ohtsuka and Yoshifumi Ninomiya and Toshitaka Oohashi",
year = "2014",
doi = "10.1007/s00011-013-0682-4",
language = "English",
volume = "63",
pages = "139--147",
journal = "Inflammation Research",
issn = "1023-3830",
publisher = "Birkhauser Verlag Basel",
number = "2",

}

TY - JOUR

T1 - Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice

AU - Maehara, Ami

AU - Nishida, Keiichiro

AU - Furutani, Masumi

AU - Matsumoto, Emi

AU - Ohtsuka, Aiji

AU - Ninomiya, Yoshifumi

AU - Oohashi, Toshitaka

PY - 2014

Y1 - 2014

N2 - 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 antibodyinduced 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.

AB - 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 antibodyinduced 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.

KW - Active targeting-liposome

KW - Arthritis

KW - Colloidal gold

KW - Drug delivery

KW - Electron microscopy

UR - http://www.scopus.com/inward/record.url?scp=84899051527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899051527&partnerID=8YFLogxK

U2 - 10.1007/s00011-013-0682-4

DO - 10.1007/s00011-013-0682-4

M3 - Article

VL - 63

SP - 139

EP - 147

JO - Inflammation Research

JF - Inflammation Research

SN - 1023-3830

IS - 2

ER -