Cell internalization of 7-ketocholesterol-containing nanoemulsion through LDL receptor reduces melanoma growth in vitro and in vivo: a preliminary report.

摘要: Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. was incorporated into a lipid core nanoemulsion. As cellular model the murine melanoma line B16F10 used. The nanoparticle (7KCLDE) uptake tumor cells displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting LDL-receptor-mediated internalization. 7KCLDE mainly cytostatic, led an accumulation polyploid cells. Nevertheless, single dose killed roughly 10% In addition, it observed dissipation transmembrane potential, evidenced with flow cytometry; presence autophagic vacuoles, visualized and quantified cytometry acridine orange; myelin figures, ultrastructural microscopy. impaired cytokenesis accompanied changes morphology fibroblastoid shape supported cytoskeletal rearrangements, as shown increased actin polymerization. injected B16 tumor-bearing mice. accumulated liver tumor. promoted >50% size reduction, enlarged necrotic area, reduced intratumoral vasculature. survival rates animals, without hematologic or toxicity. Although more pre-clinical studies should performed, our preliminary results suggested promising novel preparation for chemotherapy.