Warianty tytułu
Języki publikacji
Abstrakty
Oligonucleotides (ODNs) are short (up to 30 bases) fragments of single-stranded nucleic acids that are used as sequence specific regulators of gene expression and anti-sense based therapeutics. ODNs are frequently aggregated with particulates in order to improve their pharmacological characteristics. Complexes of ODN and lipid aggregates are among the most commonly mentioned in the literature. In order to control the formation and final properties of such aggregates, a detailed description of how ODN interacts with the lipid surface is needed. In this paper, we present the results of fluorescence measurements regarded an association of 20 base ODN, labelled with fluorescein, and a lipid surface containing various amount of positive charge. Unilamellar lipid vesicles were formed from egg phosphatidylcholine (PC) and various amounts of the cationic lipid l,2-dioleoyl-3-trimethylammonium- propane (DOTAP). It was found that about 20 mol% of DOTAP in the lipid bilayer suffices to obtain complete ODN association. This result was further confirmed via measurements performed by fluorescence correlation spectroscopy (FCS). These in turn showed that the diffusion time of labelled ODN in the presence of cationic liposomes decreases. Also, the particle number and count rate were reduced, concurring with conclusions derived from steady state fluorescence spectroscopy results.
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Opis fizyczny
p.77-84,fig.
Twórcy
autor
- Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland
autor
autor
autor
Bibliografia
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- 2.Dean, N.M., Cooper, S.R., Shanahan, W., Taylor, J. and Myers, K. Pharmacology of antisense oligonucleotides. J. Clin. Ligand Assay 23 (2000) 43-49.
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- 6.Niidome, T., Wakamatsu, M., Wada, A., Hirayama, T. and Aoyagi, H. Required structure of cationic peptide for oligonucleotid-binding and delivering into cells. J. Pept. Sci. 6 (2000) 271-279.
- 7.Fattal, E., Dubernet, C. and Couvreur, P. Liposome-based formulations for the delivery of oligonucleotides. S. T. P. Pharma Sci. 11 (2001) 31-44.
- 8.Lasic, D.D., Strey, H., Stuart, M.C.A., Podgornik, R. and Frederik, P.M. The structure of DNA-liposome complexes. J. Am. Chem. Soc. 119 (1997) 832-833.
- 9.Sternberg, B. Morphology of cationic/DNA complexes in relation to their chemical composition. J. Liposome Res. 6 (1996) 515-533.
- 10.Dongmei L. and David G.R. Binding of phosphorothioate oligonucleotides to zwitterionic liposomes. Biochim. Biophys. Acta 1563 (2002) 45-52.
- 11.Stec, W.J., Uznanski, B., Wilk, A., Hirschbeih, B.L., Fearon, K. L. and Bergot, B.J. Is (O,O-diisopropoxyphosphinothioyl)disulphide - highly efficient sulphurizing reagent for cost-effective synthesis of oligo(nucleoside phosphorothioate)s. Tetrahedron Lett. 34 (1993) 5317- 5320.
- 12.Winiski, A.P., Eisenberg, M., Langner, M. and McLaughlin, S. Fluorescent probes of electrostatic potential 1 nm from the membrane surface. Biochemistry 27 (1988) 386-392.
- 13.Thompson, N.L. Fluorescence Correlation Spectroscopy. Topics in Fluorescence Spectroscopy (Lakowicz J. R.), Plenum Press, New York, Vol. I, 337-377.
- 14.Schwille, P., Bieschke, J. and Oehlenschläger, F. Kinetic investigations by fluorescence correlation spectroscopy: The analytical and diagnostic potential of diffusion studies. Biophys. Chem. 6 (1997) 211-228.
- 15.Langner, M. and Kubica, K. Electrostatics of lipid surfaces. Chem. Phys. Lipids 101 (1999) 3-35.
- 16.Langner, M., Pruchnik, H. and Kubica, K. The effect of the lipid bilayer state on fluorescence intensity of fluorescein-PE in a saturated lipid bilayer. Z. Naturforsch. 55c (2000) 418-424.
Typ dokumentu
Bibliografia
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bwmeta1.element.agro-article-afedad9f-1d65-4fb8-9a87-67e154487155