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

Judit Reményi, Gabriella Csík, Péter Kovács, Francesca Reig, Ferenc Hudecz

Research output: Contribution to journalArticle

9 Citations (Scopus)


The 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 acid-induced 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 effect 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.

Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number3
Publication statusPublished - Mar 1 2006


  • Altered conjugate cytotoxicity
  • Daunomycin
  • Polypeptide carrier
  • Uptake of daunomycin conjugate
  • pH-dependent drug liberation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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