Abstract
Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cell-surface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol (MW 2000) lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities (1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%, and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice, AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.