Journal of Carcinogenesis & Mutagenesis

Abstract

Efficacy of Drug-Free Cationic Hybrid Liposomes Composed of L-? Dimyristoylphosphatidylcholine in Targeting Negatively Charged Cholangiocarcinoma Cell Membranes: An In Vitro and In Vivo Study

Hideaki Ichihara*, Hiromitsu Takaki, Muneaki Motomura, Masaki Okumura, Koichi Goto, Yoko Matsumoto

Cationic Hybrid Liposomes (CL) composed of 87 mol% Dimyristoylphosphatidylcholine (DMPC), 5 mol% Polyoxyethylene (21) Dodecyl Ether (C12(EO)21, also referred to as (HL21), and 8 mol% O,O’-Ditetradecanoyl-N-(α– Trimethylammonioacetyl) Diethanolamine Chloride (2C14ECl) were prepared by sonication. A clear solution of CL with a hydrodynamic diameter of 100 nm was maintained for four weeks. Cholangiocarcinoma cells exhibited a lower zeta potential than normal bile duct cells due to higher levels of negatively charged phosphatidylserine and Ganglioside 1 (GM1). Time-dependent immediate fusion of CL with cholangiocarcinoma cell membranes was confirmed using confocal microscopy. The 50% inhibitory concentration values of CL for the growth of human cholangiocarcinoma cells were markedly lower than those of DMPC and HL21 liposomes. CL-induced apoptosis of cholangiocarcinoma cells based on the propidium iodide assay using flow cytometry. The induction of apoptosis with the activation of caspase -3, -8, -9 and a decrease in the mitochondrial membrane in cholangiocarcinoma cells by CL were verified using flow cytometry. A remarkable reduction in tumor volume and weight in model mice of human cholangiocarcinoma intravenously treated with CL without drugs after the subcutaneous inoculation of cholangiocarcinoma cells was verified in vivo.

Published Date: 2024-11-25; Received Date: 2024-10-23