Development of Synthetic Peptide-Modified Liposomes with LDL Receptor Targeting Capacity and Improved Anticancer Activity

In this study, we report an active targeting liposomal formulation directed by a novel peptide (AA13) that specifically binds to the low density lipoprotein receptor (LDLR) overexpressed on acute myeloid leukemia (AML) cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of AA13-anchored liposomes on AML cells. AA13 conjugated to the distal end of DSPE-PEG2000-maleimide was incorporated into the liposomes via a postinsertion method. To study the effect of the peptide decoration and density on tumor cell targeting and internalization by AML cells (THP-1 and NB4), stealth liposomes bearing 3% (peptide/S100PC, molar ratio, LL) and 7% (peptide/S100PC, molar ratio, HL) AA13 were prepared, respectively. Higher uptake of LL (1.9- and 2.6-fold) and HL (2.3- and 3.6-fold) targeted liposomes occurred in THP-1 and NB4 cells, respectively, compared to untargeted liposomes. An LDLR inhibitor was used to confirm inhibition of the receptor-mediated cellular associat...