VCAM-1 directed immunoliposomes selectively target tumor vasculature in vivo.
Targeting the tumor vasculature and selectively modifying endothelial functions is an attractive anti-tumor strategy. We prepared polyethyleneglycol modified immunoliposomes (IL) directed against vascular cell adhesion molecule 1 (VCAM-1), a surface receptor over-expressed on tumor vessels, and investigated the liposomal targetability in vitro and in vivo. In vitro, anti-VCAM-1 liposomes displayed specific binding to activated endothelial cells under static conditions, as well as under simulated blood flow conditions. The in vivo targeting of IL was analysed in mice bearing human Colo 677 tumor xenografts 30 min and 24 h post i.v. injection. Whereas biodistribution studies using [3H]-labelled liposomes displayed only marginal higher tumor accumulation of VCAM-1 targeted versus unspecific ILs, fluorescence microscopy evaluation revealed that their localisations within tumors differed strongly. VCAM-1 targeted ILs accumulated in tumor vessels with increasing intensities from 30 min to 24 h, while control ILs accumulated in the tumor tissue by passive diffusion. ILs that accumulated in non-affected organs, mainly liver and spleen, primarily co-localised with macrophages. This is the first morphological evidence for selective in vivo targeting of tumor vessels using ILs. VCAM-directed ILs are candidate drug delivery systems for therapeutic anti-cancer approaches designed to alter endothelial function.
Gosk
Sara
S
University of Bonn, Department of Pharmacy, An der Immenburg 4, 53121 Bonn, Germany. saragosk@gmail.com <saragosk@gmail.com>
Moos
Torben
T
Gottstein
Claudia
C
Bendas
Gerd
G
D000818:Animals; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply*; D009928:Organ Specificity; D010316:Particle Size; D012235:Rhodamines; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D008081:Liposomes; D012235:Rhodamines; D019010:Vascular Cell Adhesion Molecule-1