Partitioning of europium chelate into lipid bilayer as revealed by p-terphenyl and pyrene quenching
Abstract
A fluorescence quenching method is an effective tool for obtaining important information about different
properties of biophysical and biochemical systems. In the present study quenching of fluorescent probes,
p-terphenyl, and pyrene by europium chelate were observed in phosphatidylcholine liposomes. Europium
chelates (EC) belong to a new class of potential antitumor drugs with high cytotoxic activity. These
compounds are of particular interest for biomedical investigations and diagnostics since their spectral
characteristics are optimal for a decrease of light scattering in biological patterns and background signals.
However, the application of such drugs in a free form is limited by their high toxicity and metabolic
instability. One efficient way to increase drug efficiency is based on using different drug delivery systems
such as liposomes. Highly adaptable liposome-based nanocarriers currently attract increasing attention,
because of their advantages, viz. complete biodegradability, ability to carry both hydrophilic and
lipophilic payloads and protect them from chemical degradation and transformation, increased therapeutic
index of a drug, flexibility in coupling with targeting and imaging ligands, improved pharmacodynamic
profiles compared to free drugs, etc. The present study was focused on the examination of the lipid bilayer interactions of europium chelate (here referred to as V10). Fluorescence intensity of membrane incorporated probes – pyrene and p-terphenyl – was found to decrease with increasing concentration of the drug, suggesting that V10 represents an effective quencher for these probes. This finding was explained by the drug penetration into the hydrophobic membrane core, followed by the collision between V10 and probe molecules and subsequent fluorescence quenching. The acquired fluorescence quenching data were quantitatively interpreted in terms of the dynamic quenching model.
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2. Zeimer R.C. et al. A potential method for local drug and dye delivery in the ocular vasculature // Investigative ophthalmology & Visual Sci. 1988. V. 29(7). P. 1179-1183.
3. Torchilin V.P. Recent advances with liposomes as pharmaceutical carriers // Nat. Rev. Drug Discovery. 2005. V. 4. P. 145-160.
4. Cavalcanti L.P. et al. Drug loading to lipid-based cationic nanoparticles // Nucl. Instrum. Methods Phys. Res., Sect. B. 2005. V. 238. P. 290-293.
5. Moses A.M. et al. Advancing the field of drug delivery: taking aim at cancer // Cancer Cell. 2003. V. 4. P. 337-341.
6. Gallia G.L., Brem S., Brem H. Local treatment of malignant brain tumors using implantable chemotherapeutic polymers // J Natl. Compr. Canc. Netw. 2005. V. 3(5). P. 721-728.
7. Rawat M. et al. Lipid carriers: a versatile delivery for proteins and peptides // Yakugaku Zasshi. 2008. V. 128(3). P. 269-280.
8. Shaheen S.M. et al. Liposome as a carrier for advanced drug delivery // Pak. J. Biol. Sci. 2006. V. 9(6). P. 1181-1191.
9. Yamauchi M. et al. Release of drugs from liposomes varies with particle size // Biol. Phar. Bull. 2007. V. 30(5). P. 963-966.
10. Cereda C.M.S. et al. Regional anesthesia and pain. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesis duration // Can. J. Anesth. 2006. V. 53(11). P. 1092-1097.
11. Sharma A., Sharma U.S. Liposomes in drug delivery: progress and limitations // Int. J. Pharm. 1997. V. 154 P. 123-140.
12. Kępczyński M. et al. Which physical and structural factors of liposome carriers control their drug-loading efficiency? Chem. Phys. Lipids. 2008. V. 155. P. 7-15.
13. Drummond D.C. et al. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rew. 1999. V. 51(4). P. 691-743.
14. Ladokhin A.S., Selsted M.E., White S.H. Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids // Biophys. J. 1997. V. 72. P. 794-805.
15. Word R.C., Smejtek P. Partitioning of tetrachlorophenol into lipid bilayers and sarcoplasmic reticulum: effect of length of acyl chains, carbonyl group of lipids and biomembrane structure // J. Membrane Biol. 2005. V. 203. P. 127-142.
16. Santos N.C. et al. Quantifying molecular partition into model systems of biomembranes: an emphasis on optical spectroscopic methods // Biochim. Biophys. Acta. 2003. V. 1612. P. 123-135.
17. Wang J. et al. Lateral sequestration of phosphatidylinositol 4,5-bisphosphate by the basic effector domain of myristoylated alanine-rich C kinase substrate is due to nonspecific electrostatic interactions // J. Biol. Chem. 2002. V. 277(37). P. 34401–34412.
18. Parry M.J. et al. A versatile method for determining the molar ligand-membrane partition coefficient // J. Fluoresc. 2007. V. 17. P. 97-103.
19. Lakowicz J.R., Hogen D., Omann G. Diffusion and partitioning of a pesticide, lindane, into phosphatidylcholine bilayers: a new fluorescence quenching method to study chlorinated hydrocarbo membrane interactions // Biochim. Biophys. Acta. 1977. V. 471. P. 401–411.
20. Lakowicz J.R. Principles of Fluorescent Spectroscopy, third ed. Plenum Press, New York. 2006.
21. Gudasi K.B. et al. Antimicrobial study of newly synthesized lanthanide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1,2-dihydroquinazolin-4(3H)-one // Met.-Based Drugs 2007. V. 2007. P. 1-7.
22. Rothchild R., Wyss H. NMR studies of drugs. Applications of lanthanide shift reagents to afloqualone, an axially chiral quinazolinone // Spectrosc. Lett. 1994. V. 27(2). P. 225-246.
23. Meshkova S.B. The dependence of the luminescence intensity of lanthanide complexes with β-diketones on the ligand form // J. Fluoresc. 2000. V. 10(4). P. 333-337.
24. Hemmilä I., Laitala V. Progress in lanthanides as luminescent probes // J. Fluoresc. 2005. V. 15(4). P. 529-542.
25. Pihlasalo S. et al. Liposome-based homogeneous luminescence resonance energy transfer // Anal. Biochem. 2009. V. 384. P. 231-237.
26. Zhang X., Lei X., Dai H. Synthesis and characterization of light lanthanide complexes with 5-aminosalicylic acid // Synth. React. Inorg. Met.-Org. Chem. 2004. V. 34(6). P. 1123-1134.
27. Momekov G. et al. Evaluation of the cytotoxic and pro-apoptotic activities of Eu(III) complexes with appended DNA intercalators in a panel of human malignant cell lines // Medicinal Chemistry. 2006. V. 2. P. 439-445.
28. Mui B., Chow L., Hope M.J. Extrusion technique to generate liposomes of defined size // Meth. Enzymol. 2003. V. 367. P. 3-14.
29. Jezewska M.J., Bujalowsk W. Quantitative analysis of ligand-macromolecule interactions using differential dynamic quenching of the ligand fluorescence to monitor the binding // Biophys. Chem. 1997. V. 64. P. 417-420.
30. Ahmad A. et al. Applications of the static quenching of rhodamine B by carbon nanotubes // Chem. Phys. Chem. 2009. V. 10. P. 2251-2255.
31. Vázquer J.L. et al. 6-Fluoroquinolone–liposome interactions: fluorescence quenching study using iodide // Int. J. Pharm. 1998. V. 171(1). P. 75-86.
32. Ferreira H. et al. Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study // Anal. Bioanal.Chem. 2003. V. 377. P. 293-298.
33. Lucio M. et al. Interactions between oxicams and membrane bilayers: an explanation for their different COX selectivity // Med. Chem. 2006. V. 2(5). P. 447-456.
34. Fato R. et al. Determination of partition and lateral diffusion coefficients of ubiquinones by fluorescence quenching of n-(9-anthroyloxy)stearic acids in phospholipid vesicles and mitochondrial membranes // Biochem. 1986. V. 25. P. 3378-3390.
35. Valeur B. Molecular fluorescence: principles and applications. Weinheim: Wiley-VCH. 2002.
36. Barenholz Y. et al. Lateral organization of pyrene-labeled lipids in bilayers as determined from the deviation from equilibrium between pyrene monomers and ecximers // J. Biol. Chem. 1996. V. 271(6). P. 3085-3090.
37. Yudintsev A.V. et al. Lipid bilayer interactions of Eu(III) tris-β-diketonato coordination complex // Chem. Phys. Let. 2008. V. 457. P. 417-420.
38. Mattila J.-P., Sabatini K., Kinnunen P.K.J. Oxidized phospholipids as potential novel drug targets // Biophys.J. 2007. V. 93. P. 3105-3112.
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