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Viologen-phosphorus dendrimers exhibit minor toxicity against a murine neuroblastoma cell line

Abstract

Dendrimers containing viologen (derivatives of 4,4′-bipyridyl) units in their structure have been demonstrated to exhibit antiviral activity against human immunodeficiency virus (HIV-1). It has also recently been revealed that novel dendrimers with both viologen units and phosphorus groups in their structure show different antimicrobial, cytotoxic and hemotoxic properties, and have the ability to influence the activity of cholinesterases and to inhibit α-synuclein fibrillation. Since the influence of viologen-phosphorus structures on basic cellular processes had not been investigated, we examined the impact of such macromolecules on the murine neuroblastoma cell line (N2a). We selected three water-soluble viologen-phosphorus (VPD) dendrimers, which differ in their core structure, number of viologen units and number and type of surface groups, and analyzed several aspects of the cellular response. These included cell viability, generation of reactive oxygen species (ROS), alterations in mitochondrial activity, morphological modifications, and the induction of apoptosis and necrosis. The MTT assay results suggest that all of the tested dendrimers are only slightly cytotoxic. Although some changes in ROS formation and mitochondrial function were detected, the three compounds did not induce apoptosis or necrosis. In light of these results, we can assume that the tested VPD are relatively safe for mouse neuroblastoma cells. Although more research on their safety is needed, VPD seem to be promising nanoparticles for further biomedical investigation.

Abbreviations

AO:

acridine orange

EB:

ethidium bromide

FSC:

forward scatter

H2DCFDA:

2,7-dichlorodihydrofluorescin diacetate

MTT:

3-[4,5-2-yl]-2-5-diphenyltetrazolium bromide

N2a:

murine neuroblastoma cell line

PAMAM:

polyamidoamine dendrimers

PEG:

polyethyleneglycols

PI:

propidium iodine

PPI:

polypropylenimine dendrimers

ROS:

reactive oxygen species

SSC:

side scatter

VPD:

viologen-phosphorus dendrimers

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Correspondence to Joanna Lazniewska.

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Lazniewska, J., Milowska, K., Katir, N. et al. Viologen-phosphorus dendrimers exhibit minor toxicity against a murine neuroblastoma cell line. Cell Mol Biol Lett 18, 459–478 (2013). https://doi.org/10.2478/s11658-013-0100-5

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  • DOI: https://doi.org/10.2478/s11658-013-0100-5

Key words

  • Apoptosis
  • Cytotoxicity
  • N2a cell line
  • ROS
  • Viologen-phosphorus dendrimers