Targeting of liposomes to melanoma cells with high levels of ICAM-1 expression through adhesive peptides from immunoglobulin domains.

The P(0) protein is an immunoglobulin [Ig] superfamily cell adhesion molecule from peripheral nerve myelin. Synthetic peptides derived from the P(0) protein and leukocyte function-associated antigen-1 (LFA-1) were investigated as potential ligands for targeting liposomes to intercellular adhesion molecule-1 (ICAM-1) expressing melanoma cells. Three synthetic P(0) peptides and one LFA-1 peptide were selected for linkage to liposome surfaces. P(0)-peptide-1, from the extracellular Ig-like domain, increased liposome binding to M21 (6.36-fold) and A-375 (1.85-fold) cells compared to control blank liposomes, but did not increase liposome binding to MeM 50-10 cells. P(0)-peptide-3, from the basic intracellular domain, increased binding of liposomes to all three melanoma cell lines nonspecifically due to its high content of positively charged amino acids. LFA-1- and negative control arg-gly-asp (RGD)-peptides did not affect liposome binding to M21 cells. The extent of P(0)-peptide-1-liposome binding to human melanoma cell lines correlated with the level of cellular ICAM-1 expression (r(2) = 0.868). P(0)-peptide-1-mediated targeting of liposomes might, therefore, prove useful in the development of drug delivery systems for treatment of ICAM-1 expressing malignant melanomas. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:396-404, 2002