Characterization and Anticancer Activity of a Folic Acid Conjugated and Cationic Peptide L-K6 Encapsulated Cancer-Targeting Liposomal Drug Delivery System

Cationic antimicrobial peptides (CAPs) have gained increasing attention in current anti-cancer drugs discovery due to their unique mechanisms of action and remarkable cancer cell selectivity. However, considering rapid enzymatic hydrolysis and poor stability in vivo, the further application of CAPs is limited. Encapsulation of CAPs in cancer-targeting liposome may help improve their stability and plasma half-life. We previously discovered the L-K6, a natural sourced CAP, exerts promising anticancer activity. In the present study, we modified liposome by conjugating cancer-targeting molecule folic acid (FA) and encapsulating L-K6 to construct a liposomal nano-sized cancer-targeting drug delivery system (FA-L-K6-LIP). Characterization analysis of FA-L-K6-LIP showed an encapsulation efficiency of (48.11 +/- 1.29) %, a particle size of (98.48 +/- 0.23) nm, and a Zeta potential of (- 9.05 +/- 0.17) mV. Transmission electron microscope observation revealed a sphere shape of FA-L-K6-LIP. The anticancer activity of FA-L-K6-LIP was further evaluated both in vitro and in vivo. MTT assay indicated a strong inhibiting effect of FA-L-K6-LIP against proliferation of human breast cancer MCF-7 cells in vitro. In addition, in nude mice carrying established MCF-7 xenografts, FA-L-K6-LIP specifically targeted tumor tissue and suppressed tumor growth. All these findings provide important experimental evidence for the development and clinical application of CAPs-encapsulated and FA-conjugated liposomal delivery system as potential anticancer agent in the future.