Targeting of ICAM-1-directed immunoliposomes specifically to activated endothelial cells with low cellular uptake: use of an optimized procedure for the coupling of low concentrations of antibody to liposomes

Hua, Susan, Chang, Hsin-I, Davies, Nigel M. and Cabot, Peter J. (2011) Targeting of ICAM-1-directed immunoliposomes specifically to activated endothelial cells with low cellular uptake: use of an optimized procedure for the coupling of low concentrations of antibody to liposomes. Journal of Liposome Research, 21 2: 95-105. doi:10.3109/08982101003754401


Author Hua, Susan
Chang, Hsin-I
Davies, Nigel M.
Cabot, Peter J.
Title Targeting of ICAM-1-directed immunoliposomes specifically to activated endothelial cells with low cellular uptake: use of an optimized procedure for the coupling of low concentrations of antibody to liposomes
Journal name Journal of Liposome Research   Check publisher's open access policy
ISSN 0898-2104
1532-2394
Publication date 2011-06
Sub-type Article (original research)
DOI 10.3109/08982101003754401
Volume 21
Issue 2
Start page 95
End page 105
Total pages 11
Place of publication New York, NY, United States
Publisher Informa Healthcare
Collection year 2012
Language eng
Formatted abstract
Targeted delivery of therapeutics to the endothelium is an important goal in the treatment of inflammatory diseases. The aim of this work was to exploit the overexpression of intercellular adhesion molecule-1 (ICAM-1) on activated endothelial cells for the targeting of anti-ICAM-1–coupled immunoliposomes with the intent for further use as drug carriers. Immunoliposomes were prepared from using an optimized method for the coupling of low concentrations of antibody to liposomes, thereby preventing the loss of antibody through the derivatization, extraction, and activation process. This is especially suitable for limiting ligand conjugates that are isolated or synthesized in small quantities, such as monoclonal antibodies (mAbs). To investigate the functionality of the resulting immunoliposomes, the specificity of binding and cellular internalization studies of liposomes, either nonconjugated or conjugated with mAbs to ICAM-1 or to irrelevant IgG to high endothelial venule (HEV) cells, were analyzed by fluorescence microplate spectroscopy at 4 and 37°C. Immunoliposomes specifically directed against ICAM-1 were shown to bind selectively and specifically to tumor necrosis factor alpha–activated endothelial cells in vitro, with minimal cellular internalization. This study provides a novel delivery system that has the potential for targeting therapeutics to inflammatory tissue.

Keyword Antibody conjugation
Monoclonal antibody
Intercellular adhesion molecule-1
Targeted drug delivery
Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Pharmacy Publications
 
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Created: Thu, 28 Jul 2011, 14:02:20 EST by Charna Kovacevic on behalf of School of Pharmacy