چکیده (انگلیسی):

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 cellsurface
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.