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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/14577

The effect of the structure of branched polypeptide carrier on intracellular delivery of daunomycin

AutorReményi, Judit; Csík, Gabriella; Kovács, Péter; Reig Isart, Francesca; Hudecz, Ferenc
Palabras clavePolypeptide carrier
pH-dependent drug liberation
Altered conjugate cytotoxicity
Uptake of daunomycin conjugate
Fecha de publicación18-ene-2006
CitaciónBiochimica et Biophysica Acta 1758(3): 280-289 (2006)
ResumenThe conjugate of acid labile cis-aconityl-daunomycin (cAD) with branched chain polypeptide, poly[Lys(Glui-DL-Alam)] (EAK) was very effective against L1210 leukemia in mice. However, Dau attached to a polycationic polypeptide, poly[Lys(Seri-DL-Alam)] (SAK) exhibited no in vivo antitumor effect. In order to understand this difference we have performed comparative in vitro studies to dissect properties related to interaction with the whole body (e.g., biodistribution) from those present at cellular or even molecular level. We report here (a) the kinetics of acidinduced Dau liberation, (b) interaction with DPPC phospholipid bilayer, (c) in vitro cytotoxic effect on different tumor cells, and (d) intracellular distribution in HL-60 cells of polycationic (cAD-SAK) and amphoteic (cAD-EAK) conjugates. Fluorescence properties of the two conjugates are also reported. Our findings demonstrate that the kinetics of the drug release, intracellular distribution and in vitro cytotoxic effect are rather similar, while the ef ect on DPPC phospholipid bilayer and fluorescence properties of the two conjugates are not the same. We also found that the in vitro cytotoxicity is cell line dependent. These observations suggest that the structure of the polypeptide carrier could have marked influence on drug uptake related events.
Descripción10 pages, 7 figures.-- PMID: 16500616 [PubMed].-- Printed version published Mar 2006.-- Issue title: "Mechanisms of Carrier-Mediated Intracellular Delivery of Therapeutics".
Versión del editorhttp://dx.doi.org/10.1016/j.bbamem.2005.12.008
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