The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells
Yang Zeng, Yoshika Kurokawa, Tin-Tin Win-Shwe, Qin Zeng, Seishiro Hirano, Zhenya Zhang, Hideko Sone
Author information
  • Yang Zeng

    Center for Environmental Risk Research, National Institute for Environmental Studies
    Graduate School of Life and Environmental Sciences, University of Tsukuba

  • Yoshika Kurokawa

    Center for Environmental Risk Research, National Institute for Environmental Studies

  • Tin-Tin Win-Shwe

    Graduate School of Life and Environmental Sciences, University of Tsukuba
    Center for Environmental Health Sciences, National Institute for Environmental Studies

  • Qin Zeng

    Center for Environmental Risk Research, National Institute for Environmental Studies

  • Seishiro Hirano

    Center for Environmental Risk Research, National Institute for Environmental Studies

  • Zhenya Zhang

    Graduate School of Life and Environmental Sciences, University of Tsukuba

  • Hideko Sone

    Center for Environmental Risk Research, National Institute for Environmental Studies

Corresponding author

ORCID
Keywords: PAMAM dendrimers, Human neural progenitor cells, Neuronal development, Particle characteristic
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Supplementary material

2016 Volume 41 Issue 3 Pages 351-370

Details
  • Published: June 01, 2016 Received: June 26, 2015 Released on J-STAGE: May 17, 2016 Accepted: February 29, 2016 Advance online publication: - Revised: -
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Abstract
Polyamidoamine (PAMAM) dendrimers have potential for biological applications as delivery systems for genes, drugs, and imaging agents into the brain, but their developmental neurotoxicity remains unknown. We investigated the effects of PAMAM dendrimers with various surface functional groups and multiple generationson neuronal differentiation using human neural progenitor cells at an equal mass concentration. Only PAMAM dendrimers containing amine (NH2) surface groups at concentrations of 10 μg/mL significantly reduced cell viability and neuronal differentiation, compared with non-amine-terminated dendrimers. PAMAM-NH2 with generation (G)3, G4, G5 G6, and G7 significantly decreased cell viability and inhibited neuronal differentiation from a concentration of 5 μg/mL, but G0, G1, and G2 dendrimers did not have any effect at this concentration. Cytotoxicity indices of PAMAM-NH2 dendrimers at 10 μg/mL correlated well with the zeta potentials of the particles. Surface group density and particle number in unit volume is more important characteristic than particle size to influence cytotoxicity for positive changed dendrimers. PAMAM-50% C12 at 1 μg/mL altered the expression level of the oxidative stress-related genes, ROR1, CYP26A1, and TGFB1, which is a DNA damage response gene. Our results indicate that PAMAM dendrimer exposure may have a surface charge-dependent adverse effect on neuronal differentiation, and that the effect may be associated with oxidative stress and DNA damage during development of neural cells.
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© 2016 The Japanese Society of Toxicology
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