Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions

Gabriella Nyitrai, Orsolya Kékesi, Ildikó Pál, Péter Keglevich, Zsuzsánna Csíki, Péter Fügedi, Ágnes Simon, Ilona Fitos, Krisztina Németh, Júlia Visy, Gábor Tárkányi, Julianna Kardos

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We report for the first time on neuronal signaling for the evaluation of interactions between native plasmamembrane and polyamidoamine (PAMAM) dendrimers. Generation 5 polycationic (G5-NH2), novel β-D-glucopyranose- conjugated G5-NH2 and generation 4.5 polyanionic (G4.5-COONa) polyamidoamine (PAMAM) dendrimers (1-0.0001 mg/ml) were applied in acute brain slices. Functional toxicity assessments-validated by fluorescence imaging of dead cells-were performed by employing electrophysiological indicators of plasma membrane breakdown and synaptic transmission relapse. Irreversible membrane depolarization and decrease of membrane resistance predicted substantial functional neurotoxicity of unmodified G5-NH2, but not of the G4.5-COONa PAMAM dendrimers. Model calculations suggested that freely moving protonated NH2 groups of terminal monomeric units of PAMAM dendrimers may be able directly destroy the membrane or inhibit important K+ channel function via contacting the positively charged NH2. In accordance, conjugation of surface amino groups by β-D-glucopyranose units reduced functional neurotoxicity that may hold great potential for biomedical applications.

Original languageEnglish
Pages (from-to)576-586
Number of pages11
JournalNanotoxicology
Volume6
Issue number6
DOIs
Publication statusPublished - Sep 1 2012

Keywords

  • Functional neurotoxicity indicators
  • Imaging cell death
  • Molecular simulation
  • Polycationic and polyanionic PAMAM dendrimers
  • β-D-glucopyranose-conjugation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

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