Complementary targeting of liposomes to IL-1? and TNF-? activated endothelial cells via the transient expression of VCAM1 and E-selectin

Abstract

Inflammation is in part defined by the transient upregulation of cell adhesion molecules on the surface of endothelial cells (ECs) in response to cytokines. We hypothesized that liposomes with a complementary surface presentation of antibodies to the pattern of molecules on the EC surface may enhance targeting. We quantified the expression of vascular cell adhesion molecule-1 (VCAM1) and endothelial leukocyte cell adhesion molecule-1 (E-selectin) on ECs upon exposure to either tumor necrosis factor-α (TNF-α) or interleukin-1α (IL-1α) as a function of time. Liposomes, composed of 95 mol% dioleoyl phosphatidylcholine (DOPC) and 5 mol% dodecanyl phosphatidylethanolamine (N-dod-PE), were prepared by conjugating different molar ratios of antibodies against VCAM1 (aVCAM1) and E-selectin (aE-selectin). Increased binding was observed when immunoliposomes complemented the presentation of VCAM1:E-selectin expressed on TNF-α activated ECs. The 1:1 aVCAM1:aE-selectin liposomes had maximal binding at both 6 and 24 h on IL-1α activated ECs due to differences in molecular organization. The results demonstrate that liposomes targeting to inflamed endothelium may be optimized by exploiting the dynamic expression of VCAM1 and E-selectin on the EC surface.