Skip to main content
Log in

Europium Coordination Complexes as Potential Anticancer Drugs: Their Partitioning and Permeation Into Lipid Bilayers as Revealed by Pyrene Fluorescence Quenching

  • ORIGINAL PAPER
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

The present study was undertaken to evaluate the membrane-associating properties of a series of novel antitumor agents, Eu(III) coordination complexes (EC), using the pyrene fluorescence quenching as an analytical instrument. Analysis of EC-induced decrease in pyrene fluorescence intensity in terms of partition and solubility-diffusion models allowed us to evaluate the partition and permeation coefficients of the examined compounds into the lipid vesicles prepared from zwitterionic lipid phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) and anionic lipid cardiolipin (CL). The drug-lipid interactions were found to have the complex nature determined by both EC structure and lipid bilayer composition. High values of the obtained partition and permeation coefficients create the background for the development of EC liposomal formulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bünzli JG, Piguet C (2005) Taking advantage of luminescent lanthanide ions. Chem Soc Rev 34:1048–1077

    Article  PubMed  Google Scholar 

  2. Vogler A, Kunkely H (2006) Excited state properties of lanthanide complexes: beyond ff states. Inorg Chim Acta 359:4130–4138

    Article  CAS  Google Scholar 

  3. Maas H, Currao A, Calzaferri G (2002) Encapsulated lanthanides as luminescent materials. Angew Chem Int Ed 41:2495–2497

    Article  CAS  Google Scholar 

  4. Orcutt KM, Jones WC, McDonald A, Schrock D, Wallace KJ (2010) A lanthanide-based chemosensor for bioavailable Fe3+ using a fluorescent siderophore: an assay displacement approach. Sensors 10:1326–1337

    Article  PubMed  CAS  Google Scholar 

  5. Yuan J, Wang G (2005) Lanthanide complex-based fluorescence label for time-resolved fluorescence bioassay. J Fluoresc 15:559–568

    Article  PubMed  CAS  Google Scholar 

  6. Bakker BH, Goes M, Hoebe N, van Ramesdonk HJ, Verhoeven JW, Werts MHV, Hofstraat JW (2000) Luminescent materials and devices: lanthanide azatriphenylene complexes and electroluminescent charge transfer systems. Coord Chem Rev 208:3–16

    Article  CAS  Google Scholar 

  7. Dean Sherry A (1989) Lanthanide chelates as magnetic resonance imaging contrast agents. J Less Common Met 149:133–141

    Article  Google Scholar 

  8. Thompson K, Orvig C (2006) Lanthanide compounds for therapeutic and diagnostic applications. Chem Soc Rev 35:499–499

    Article  PubMed  CAS  Google Scholar 

  9. Kostova I (2005) Lanthanides as anticancer drugs. Curr Med Chem Anticancer Agents 5:591–602

    Article  PubMed  CAS  Google Scholar 

  10. Evans CH (1983) Interesting and useful biochemical properties of lanthanides. Trends Biochem Sci 8:445–449

    Article  CAS  Google Scholar 

  11. Momekov G, Deligeorgiev T, Vasilev A, Peneva K, Konstantinov S, Karaivanova M (2006) Evaluation of the cytotoxic and pro-apoptotic activities of Eu(III) complexes with appended DNA intercalators in a panel of human malignant cell lines. Med Chem 2:439–445

    Article  PubMed  CAS  Google Scholar 

  12. Chonn A, Cullis P (1995) Recent advances in liposomal drug-delivery systems. Curr Opin Biotechnol 6:698–708

    Article  PubMed  CAS  Google Scholar 

  13. Maurer N, Fenske D, Cullis P (2001) Developments in liposomal drug delivery systems. Expert Opin Biol Ther 1:1–25

    Article  Google Scholar 

  14. Mickova A, Buzgo M, Benada O, Rampichova M, Fisar Z, Filova E, Tesarova M, Lukas D, Amler E (2012) Core/shell nanofibers with embedded liposomes as a drug delivery system. Biomacromolecules 13:952–962

    Article  PubMed  CAS  Google Scholar 

  15. Ladokhin AS, Selsted ME, White SH (1997) Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids. Biophys J 72:794–805

    Article  PubMed  CAS  Google Scholar 

  16. Word RC, Smejtek P (2005) 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 203:127–142

    Article  CAS  Google Scholar 

  17. Santos NC, Prieto M, Castanho M (2003) Quantifying molecular partition into model systems of biomembranes: an emphasis on optical spectroscopic methods. Biochim Biophys Acta 1612:123–135

    Article  PubMed  CAS  Google Scholar 

  18. Wang J, Gambhir A, Hangyas-Mihalyne G, Murray D, Golebiewska U, McLaughlin S (2002) 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 277:34401–34412

    Article  PubMed  CAS  Google Scholar 

  19. Lakowicz JR (2006) Principles of fuorescence spectroscopy. Plenum Press, New York

    Book  Google Scholar 

  20. Lakowicz JR, Hogen D, Omann G (1977) Diffusion and partitioning of a pesticide, lindane, into phosphatidylcholine bilayers: a new fluorescence quenching method to study chlorinated hydrocarbo membrane interactions. Biochim Biophys Acta 471:401–411

    Article  PubMed  CAS  Google Scholar 

  21. Mui B, Chow L, Hope MJ (2003) Extrusion technique to generate liposomes of defined size. Meth Enzymol 367:3–14

    Article  PubMed  CAS  Google Scholar 

  22. Bartlett G (1959) Phosphorus assay in column chromatography. J Biol Chem 234:466–468

    PubMed  CAS  Google Scholar 

  23. Mathai J, Tristam-Nagle S, Nagle J, Zeidel M (2008) Structural determinants of water permeability through the lipid membrane. J Gen Physiol 131:69–76

    Article  PubMed  CAS  Google Scholar 

  24. Dobretsov GE (1989) Fluorescent probes for the cell, membrane and lipoprotein studies. Nauka, Moscow

    Google Scholar 

  25. Inada T, Funasaka Y, Kikuchi K, Takahashi Y, Ikeda H (2006) Electron-transfer fluorescence quenching of aromatic hydrocarbons by europium and ytterbium ions in acetonotrile. J Phys Chem A 110:2595–2600

    Article  PubMed  CAS  Google Scholar 

  26. Nakamura T, Kira A, Imamura M (1982) Enhancement of the intersystem crossing of pyrene by metal ions in sodium dodecyl sulfate micelle solutions. J Phys Chem 86:3359–3363

    Article  CAS  Google Scholar 

  27. Lee J, Carraway E, Schlautman M, Yim S, Herbert B (2004) Chaarcterizing pyrene-Ag+ exciplex formation in aqueous and ethanolic solutions. J Photochem Photobiol A 167:141–148

    Article  CAS  Google Scholar 

  28. Dederen J, Auweraer M, Schryver F (1981) Fluorescence quecnhing of solubilized pyrene and pyrene derivatives by metal ions in SDS micelles. J Phys Chem 85:1198–1202

    Article  CAS  Google Scholar 

  29. Lemmetyinen H, Yliperttula M, Mikkola J, Kinnunen P (1989) Quenching of fluorescence of pyrene-substituted lecithin by tetracyanoquinodimethane in liposomes. Biophys J 55:885–895

    Article  PubMed  CAS  Google Scholar 

  30. de Paula E, Schreier S (1995) Use of a novel method for determination of partition coefficients to compare the effect of local anesthetics on membrane structure. Biochim Biophys Acta 1240:25–33

    Article  PubMed  Google Scholar 

  31. Zhang J, Hadlock T, Gent A, Strichartz G (2007) Tetracaine-membrane interactions: effects of lipid composition and phase on drug partitioning, location, and ionization. Biophys J 92:3988–4001

    Article  PubMed  CAS  Google Scholar 

  32. De Castro B, Gameiro P, Lima J, Matos C, Reis S (2001) Location and partition coefficients of anti-inflammatory drugs in EPC liposomes. A fluorescence quenching study using n-(9-anthroyloxy)-stearic probes. Colloids Surf A 190:205–212

    Article  Google Scholar 

  33. Takegami S, Kitamura K, Kitade T, Takashima M, Ito M, Nakagawa E, Sone M, Sumitani R, Yasuda Y (2005) Effects of phosphatidylserine and phosphatidylethanolamine content on partitioning of triflupromazine and chlorpromazine between phosphatidylcholine-aminophospholipid bilayer vesicles and water studied by second-derivative spectrophotometry. Chem Pharm Bull 53:147–150

    Article  PubMed  CAS  Google Scholar 

  34. Avdeef A (2003) Absorption and drug development. Wiley, New Jersey

    Book  Google Scholar 

  35. Sandhya KV, Devi G, Mathew S (2008) Liposomal formulations of serratiopeptidase: in vitro studies using PAMPA and Caco-2 models. Mol Pharm 5:92–97

    Article  Google Scholar 

  36. Pasenkiewicz-Gierula M, Rog T, Kitamura K, Kusumi A (2000) Cholesterol effects on the phosphatidylcholine bilayer polar region: a molecular simulation study. Biophys J 78:1376–1389

    Article  PubMed  CAS  Google Scholar 

  37. Kinnunen PKJ, Koiv A, Lehtonen JYA, Mustonen P (1994) Lipid dynamics and peripheral interactions of proteins with membrane surfaces. Chem Phys Lett 73:181–207

    CAS  Google Scholar 

  38. Marrink SJ, Sok RM, Berendsen HJC (1996) Free volume properties of a simulated lipid membrane. J Chem Phys 104:9090–9099

    Article  CAS  Google Scholar 

  39. Merkle H, Subczynski WK, Kusumi A (1987) Dynamic fluorescence quenching studies on lipid mobilities in phosphotidylcholine-cholesterol membranes. Biochim Biophys Acta 897:238–348

    Article  PubMed  CAS  Google Scholar 

  40. Bittman R, Blau L (1972) The phospholipid-cholesterol interaction. Kinetics of water permeability in liposomes. Biochemistry 11:4831–4839

    Article  PubMed  CAS  Google Scholar 

  41. Bach D, Miller IR (1998) Hydration of phospholipid bilayers in the presence and absence of cholesterol. Biochim Biophys Acta 1368:216–224

    Article  PubMed  CAS  Google Scholar 

  42. Rog T, Pasenkiewicz-Gierula M (2001) Cholesterol effects on the phosphatidylcholine bilayer nonpolar region: a molecular simulation study. Biophys J 81:2190–2202

    Article  PubMed  CAS  Google Scholar 

  43. Demel RA, de Kruijff B (1976) The function of sterols in membranes. Biochim Biophys Acta 457:109–132

    Article  PubMed  CAS  Google Scholar 

  44. van Balen G, Martinet C, Caron G, Bouchard G, Reist M, Carrupt PA, Fruttero R, Gasco A, Testa B (2004) Liposome/water lipophilicity: methods, information content, and pharmaceutical applications. Med Res Rev 3:299–324

    Article  Google Scholar 

  45. Giaginis C, Tsantili-Kakoulidou A (2008) Alternative measure of lipophilicity: from octanol-water partitioning to IAM retention. J Pharm Sci 97:2984–3004

    Article  PubMed  CAS  Google Scholar 

  46. Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY, Prokopenko VV (2005) Virtual computational chemistry laboratory—design and description. J Comput Aid Mol Des 19:453–463

    Article  CAS  Google Scholar 

  47. Tetko IV (2005) Computing chemistry on the web DOI:10.1016/S1359-6446(05)03584-1. Drug Discov Today 10:1497–1500

    Article  PubMed  Google Scholar 

  48. Camenisch G, Folkers G, van de Waterbeemd H (1998) Shapes of membrane permeability-lipophilicity curves: extention of theoretical models with an aqueous pore pathway. Eur J Pharm Sci 6:325–329

    PubMed  CAS  Google Scholar 

  49. Camenisch G, Folkers G, van de Waterbeemd H (1996) Review of theoretical passive drug absorption models: historical background, recent developments and limitations. Pharm Acta Helv 71:309–327

    Article  PubMed  CAS  Google Scholar 

  50. Ioffe VM, Gorbenko GP (2005) Lysozyme effect on structural state of model membranes as revealed by pyrene excimerization studies. Biophys Chem 114:199–204

    Article  PubMed  CAS  Google Scholar 

  51. Shibata A, Ikawa K, Shimooka T, Terada H (1994) Significant stabilization of the phosphatidylcholine bilayer structure by incorporation of small amounts of cardiolipin. Biochim Biophys Acta 1192:71–78

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the grant from Fundamental Research State Fund (project number F.41.4/014) and young scientist award by the President of Ukraine to VT (project number GP/F32/109).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Valeriya Trusova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trusova, V., Yudintsev, A., Limanskaya, L. et al. Europium Coordination Complexes as Potential Anticancer Drugs: Their Partitioning and Permeation Into Lipid Bilayers as Revealed by Pyrene Fluorescence Quenching. J Fluoresc 23, 193–202 (2013). https://doi.org/10.1007/s10895-012-1134-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-012-1134-1

Keywords

Navigation