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.
Highlights
The highly branched polymers called dendrimers have several unique features, including monodispersity, multivalency, and precisely determined mass, size, shape and architecture [1, 2]
At the highest tested concentration (20 μM), VPD1 and VPD3 caused a comparable decrease in cell viability, which amounts to 72.7% and 74.8% of the control respectively, while VPD2 reduced the percentage of viable cells to only 80.3% of the control
We demonstrated that the reactive oxygen species (ROS) level in murine neuroblastoma cell line (N2a) cells after viologen-phosphorus dendrimers (VPD) treatment falls below the control (Fig. 3)
Summary
The highly branched polymers called dendrimers have several unique features, including monodispersity, multivalency, and precisely determined mass, size, shape and architecture [1, 2] These special characteristics make them an attractive object of research in terms of their interactions with biological systems. All of the dendrimers showed good antimicrobial activity against the Grampositive bacteria Staphylococcus aureus These compounds demonstrated potential against neurodegenerative disorders. Other than the results of simple cytotoxicity assays, there have been no reports on the influence of viologen-phosphorus structures on the cell condition and basic functions. This inclined us to continue studies on VPD cytotoxicity and examine the impact on murine neuroblastoma cells (N2a) of three of the eight studied by Ciepluch et al [26]. We investigated several aspects of the cellular response, including cell viability, generation of reactive oxygen species (ROS), alterations in mitochondrial function, morphological modifications, and the induction of apoptosis and necrosis
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