Oleic acid-embedded nanoliposome as a selective tumoricidal agent

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human alpha-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (Liposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127 nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2 nM LIMLET, respectively, whereas the LD50 of Vero was 5.7 nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments. (C) 2016 Elsevier B.V. All rights reserved.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2008-0061891). Some authors (SJ, SL, HL, JY) were inspired by the Capstone Design project of Hanyang University