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.
Jaafari
M R
MR
College of Pharmacy and Nutrition University of Saskatchewan, 110 Science Place, Saskatoon, SK, Canada, S7N 5C9.
Foldvari
M
M
D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism* / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008024:Ligands; D008081:Liposomes / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D007136:Immunoglobulins; D008024:Ligands; D008081:Liposomes; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1