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Immunoliposomes That Target Endothelium In Vitro Are Dependent on Lipid Raft Formation

Summary: Immunoliposomes That Target Endothelium In Vitro Are
Dependent on Lipid Raft Formation
Rico C. Gunawan and Debra T. Auguste*
School of Engineering and Applied Sciences, HarVard UniVersity,
Cambridge, Massachusetts 02138
Received December 16, 2009; Revised Manuscript Received July 3, 2010; Accepted July 28, 2010
Abstract: Lipid rafts are plasma membrane microdomains rich in cholesterol, sphingolipids,
and cell surface receptors. Recent studies demonstrated the upregulation and localization of
two receptors, intercellular cell adhesion molecule-1 (ICAM, CD54) and endothelial leukocyte
adhesion molecule-1 (E-selectin, CD64E), within lipid raft microdomains of inflamed or injured
endothelial cells (ECs). We hypothesized that the localization of ICAM and E-selectin within
lipid rafts may be essential for drug delivery vehicles labeled with antibodies against ICAM
(aICAM) and E-selectin (aE-selectin). To eliminate localization of cell surface receptors, ECs
were treated with a cholesterol depleting drug, methyl- -cyclodextrin. We also tested if antibody
mobility and the ratio of aICAM to aE-selectin on immunoliposomes influenced binding to lipid-
raft-depleted cells. Liposomes were prepared from either 1,2-dioleoyl-sn-glycero-3-phosphati-
dylcholine (DOPC, C18:1, Tm ) -20 C) or 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine
(DPPC, C16:0, Tm ) 42 C) which are in the liquid crystalline and gel phase at 37 C, respectively.
Mobility and the aICAM:aE-selectin ratio influenced cellular binding only when lipid rafts form.
In the absence of lipid rafts, cellular binding of both DOPC and DPPC immunoliposomes was


Source: Auguste, Debra T. - School of Engineering and Applied Sciences, Harvard University


Collections: Materials Science; Biology and Medicine