Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (3): 447-453.doi: 10.1007/s40242-017-6303-y

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Influence of Metal Cations and Cholesterol on Lipid-amphotericin Membrane

WANG Juan1,2, SUN Runguang2, HAO Changchun2, LI Tuo1, TIAN Yuan1, ZHANG Lei2   

  1. 1. Engineering Technology Research Center of Controllable Neutron Source and Its Application, Department of Applied Statistics and Science, Xijing University, Xi'an 710123, P. R. China;
    2. Laboratory of Biophysics and Biomedicine, College of Physics and Information Technology, Shaanxi Normal University, Xi'an 710119, P. R. China
  • Received:2016-07-14 Revised:2016-11-21 Online:2017-06-01 Published:2017-04-05
  • Contact: WANG Juan,E-mail:wjbiophysics@yeah.net E-mail:wjbiophysics@yeah.net
  • Supported by:

    Supported by the National Natural Science Foundation of China(No.21402114).

Abstract:

Amphotericin B(AmB) has been widely used in antifungal therapy. AmB molecules combine with cholesterol to form pores that can be toxic to human cells, thus greatly limiting its clinical application. The interaction between AmB and the cell membrane may be influenced by potassium, sodium and calcium ions. In this study, the bilayer in large unilamellar lipid-drug liposomes with or without cholesterol was employed as a model membrane. N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine(NBD-PE) and 1-palmi-toyl-2-[6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminodoclecanoyl]-sn-glysero-3-phosphocholine(6-NBD-PC) are two kinds of fluorescent lipid probes, and the NBD group is attached to the polar lipid headgroup in the former, but to the sn-2 fatty acyl chain in the latter. The effect of these metal cations on the lipid-drug membrane was monitored by red edge excitation shift(REES), fluorescence polarization, and the fluorescence lifetime of lipid probes in hydrophilic and hydrophobic areas of the membrane. These ions have different effects on the lipid-AmB membrane. Cholesterol can strengthen the packing ability of the membrane, which is influenced differently by potassium, sodium and calcium ions. Moreover, the influence of these ions on the membrane may be relative to the method of ion transportation through the membrane. This study is significant to understand the reduction of AmB's cellular toxicity.

Key words: Amphotericin B, NBD-labeled lipid, Red edge excitation shift, Metal cation, Fluorescence polarization