Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions

G. Nyitrai, Orsolya Kékesi, Ildikó Pál, Péter Keglevich, Zsuzsánna Csíki, Péter Fügedi, A. Simon, I. Fitos, Krisztina Németh, J. Visy, G. Tárkányi, J. 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 2012

Fingerprint

Dendrimers
Toxicity
Membranes
Optical Imaging
Depolarization
Cell membranes
Synaptic Transmission
Brain
Fluorescence
Cell Membrane
Imaging techniques
Recurrence
Poly(amidoamine)

Keywords

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

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

Cite this

Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions. / Nyitrai, G.; Kékesi, Orsolya; Pál, Ildikó; Keglevich, Péter; Csíki, Zsuzsánna; Fügedi, Péter; Simon, A.; Fitos, I.; Németh, Krisztina; Visy, J.; Tárkányi, G.; Kardos, J.

In: Nanotoxicology, Vol. 6, No. 6, 09.2012, p. 576-586.

Research output: Contribution to journalArticle

Nyitrai, G. ; Kékesi, Orsolya ; Pál, Ildikó ; Keglevich, Péter ; Csíki, Zsuzsánna ; Fügedi, Péter ; Simon, A. ; Fitos, I. ; Németh, Krisztina ; Visy, J. ; Tárkányi, G. ; Kardos, J. / Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions. In: Nanotoxicology. 2012 ; Vol. 6, No. 6. pp. 576-586.
@article{28398f2b679544f2b7dad1fa760181f3,
title = "Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions",
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.",
keywords = "β-D-glucopyranose-conjugation, Functional neurotoxicity indicators, Imaging cell death, Molecular simulation, Polycationic and polyanionic PAMAM dendrimers",
author = "G. Nyitrai and Orsolya K{\'e}kesi and Ildik{\'o} P{\'a}l and P{\'e}ter Keglevich and Zsuzs{\'a}nna Cs{\'i}ki and P{\'e}ter F{\"u}gedi and A. Simon and I. Fitos and Krisztina N{\'e}meth and J. Visy and G. T{\'a}rk{\'a}nyi and J. Kardos",
year = "2012",
month = "9",
doi = "10.3109/17435390.2011.591511",
language = "English",
volume = "6",
pages = "576--586",
journal = "Nanotoxicology",
issn = "1743-5390",
publisher = "Informa Healthcare",
number = "6",

}

TY - JOUR

T1 - Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions

AU - Nyitrai, G.

AU - Kékesi, Orsolya

AU - Pál, Ildikó

AU - Keglevich, Péter

AU - Csíki, Zsuzsánna

AU - Fügedi, Péter

AU - Simon, A.

AU - Fitos, I.

AU - Németh, Krisztina

AU - Visy, J.

AU - Tárkányi, G.

AU - Kardos, J.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - β-D-glucopyranose-conjugation

KW - Functional neurotoxicity indicators

KW - Imaging cell death

KW - Molecular simulation

KW - Polycationic and polyanionic PAMAM dendrimers

UR - http://www.scopus.com/inward/record.url?scp=84871909880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871909880&partnerID=8YFLogxK

U2 - 10.3109/17435390.2011.591511

DO - 10.3109/17435390.2011.591511

M3 - Article

C2 - 21688971

AN - SCOPUS:84871909880

VL - 6

SP - 576

EP - 586

JO - Nanotoxicology

JF - Nanotoxicology

SN - 1743-5390

IS - 6

ER -