Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions
| Autor: | Júlia Visy, Orsolya Kékesi, Péter Fügedi, Gábor Tárkányi, Ilona Fitos, Gabriella Nyitrai, Zsuzsánna Csíki, Krisztina Németh, Julianna Kardos, Péter Keglevich, Ágnes Simon, Ildikó Pál |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Dendrimers Fluorescence-lifetime imaging microscopy Materials science Stereochemistry Neurotoxins Biomedical Engineering Molecular Dynamics Simulation Neurotransmission Toxicology Hippocampus Synaptic Transmission Membrane Potentials chemistry.chemical_compound Dendrimer medicine Animals Rats Wistar Nuclear Magnetic Resonance Biomolecular Fluorescent Dyes Neurons Cell Death Cell Membrane Neurotoxicity Depolarization medicine.disease Rats Electrophysiology Glucose Monomer Membrane chemistry Biophysics |
| Zdroj: | Nanotoxicology. 6:576-586 |
| ISSN: | 1743-5404 1743-5390 |
| DOI: | 10.3109/17435390.2011.591511 |
| Popis: | 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-NH(2)), novel β-D-glucopyranose-conjugated G5-NH(2) 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-NH(2), but not of the G4.5-COONa PAMAM dendrimers. Model calculations suggested that freely moving protonated NH(2) 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 NH(2). In accordance, conjugation of surface amino groups by β-D-glucopyranose units reduced functional neurotoxicity that may hold great potential for biomedical applications. |
| Databáze: | OpenAIRE |
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