Abstract

Delivering anticancer drugs to tumor tissues with high specificity to realize minimal adverse effects is currently the main research focus of cancer treatment. N ε -acyl lysine methyl esters (N ε -lys) have the potential to serve as novel and safe anticancer agents owing to their pH-responsive membrane-disruptive activity and non-toxic metabolic products. In this study, we synthesized three N ε -lys with different hydrophobic chain lengths and evaluated their cytotoxicity to cancer and normal cells. One of the compounds with an acyl chain of 14 carbon atoms (MKM) showed moderate cytotoxicity and was delivered to cancer cells encapsulated in liposomes (MKM-LP). We additionally modified the liposomes with folate and PEG as a cancer-targeting drug delivery system (FA-PEG-MKM-LP) to enhance the cell selectivity. We tested the difference in the cellular uptake of liposomes between a folate receptor-positive human ovarian cancer cell line (SKOV3) and a healthy human ovary epithelial cell line (IOSE). The experimental results showed that FA-PEG-MKM-LP had low cytotoxicity to IOSE and higher cancer-targeting ability than other tested liposomes. Fluorescence imaging of dead cells and a LDH release assay further demonstrated that the cytotoxicity of FA-PEG-MKM-LP possessed time- and dose-dependent activity and specificity to cancer cells. These results lay a foundation for the development of N ε -lys as a promising anticancer drug.