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Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration

Item Type:Article
Title:Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration
Creators Name:Koklic, T. and Zeisig, R. and Sentjurc, M.
Abstract:We have investigated interaction of alkyphospholipid (APL) liposomes consisting of 1,1-dimethylpiperidin-1-ium-4-yl) octadecyl phosphate (OPP) and different concentrations of cholesterol (CH) with human MT-3 breast-cancer cells using electron paramagnetic resonance method (EPR) with advanced characterization of EPR spectra of spin labeled liposome membranes. After incubation of OPP liposomes with MT-3 cells, a reduction of liposome entrapped, water soluble spin-probe tempocholine (ASL) was observed, indicating that ASL is released from liposomes and is reduced by oxy-redoxy systems inside the cells. This process is fast if cholesterol content in the bilayer was 29 or 45 mol%, whereas at 56 mol% cholesterol the process is almost stopped. The rate of spin-probe reduction in first 10 min after incubation with cells is even faster as for the free ASL, indicating that liposomes with low amount of cholesterol accelerate penetration of ASL into the cells. A faster release of hydrophilic material from liposomes with low cholesterol content coincides with the presence of domains with highly disordered alkyl chain motion that disappears at 50 mol% of cholesterol. We propose that these highly fluid domains are responsible for interaction of OPP liposomes with cells and fast release of the entrapped material into the cells. These results suggest that micelles are not the only reason for cytotoxic effect of OPP liposom formulations, as it was suggested before. OPP in liposomes, containing 45 mol% cholesterol or less, also contributes to the cytotoxic effect, due to their fast interaction with breast-cancer cells.
Keywords:Liposome, Liposome-Cell Interaction, Electron Paramagnetic Resonance, Cholesterol, Alkylphospholipid, Breast-Cancer Cell, Membrane Domain, Spin Label
Source:Biochimica et Biophysica Acta - Biomembranes
Publisher:Elsevier (The Netherlands)
Page Range:2682-2689
Date:December 2008
Official Publication:https://doi.org/10.1016/j.bbamem.2008.08.024
PubMed:View item in PubMed

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