Liposomes integrins

Hdlig P, et al. Novel RGD lipopeptides for the targeting of liposomes to integrin-expressing endothelial and melanoma cells. Protein Eng 2004 17 433. 

Integrin receptor-binding peptides have been used to enhance liposome binding, uptake, and expression (25,47 9). The inclusion of an 0(5pi integrin-targeted peptide into a liposomal complex enhanced transfection efficiency four- to five-fold in Jurkat cells and 10- to 13-fold in TF-1 cells (48). Confocal and electron microscopy revealed that the mechanism of cell entry conferred by RGD peptides on liposomes is predominantly by clathrin-coated endocytosis rather than by phagocytosis (50). 

Fig. 20. Targeting of the endothelial integrin a P3 as a specific angiogenesis marker. The receptor is recognized by a biotinylated antibody that is then bound by an avidin moiety bearing a Gd(III) loaded liposome.

For a proof of concept, Meinecke et aV reinvestigated this interaction by STD spectroscopy on liposome, embedded a bPs integrin. Recently, a further example... 

First, B16BL6 cells were co-injected into a tail vein of mice with either sLe -incorporated liposomes, which may bind to selectins, or with an Arg-Gly-Asp RGD-related peptide, DGRGDS conjugated with trimesic acid [Ar(GRGDS)3], which is known to suppress interaction with certain integrins. Both sLe -liposome and RGD-related peptide suppressed actual metastasis of B16BL6 cells to the lungs. 

FIGURE 5. Adhesion of BL6 cells to mouse ECs is based on interaction of GM3 (expressed on BL6 cells) with Gg3 or LacCer (expressed on ECs). (A, B) Laminar flow dynamic adhesion system. Wall shear stress was calculated as described by Lawrence et al. (1990). One of the parallel plates was coated with Gg3-liposome, LacCer-liposome, FN, or laminin (LN), and BL6 cells suspended in medium were passed through the laminar flow chamber. See Kojima etal. (1992c) for experimental details. Adhesion based on Gg3 or LacCer predominated over that based on FN or LN, regardless of shear stress. (C) Static adhesion system. FN- or LN-dependent adhesion became obvious only after 30 min of incubation. In contrast, Gg3- or LacCer-dependent adhesion were obvious at 20 min. These results suggest that there is a longer lag time for integrin-based cell adhesion compared to adhesion based on carbohydrate-carbohydrate interaction, in a static system. 

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