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.

Evaluation and Elucidation of DNA‐Containing Viologen Dendrimer Complex Formation

“…[15] Furthermore, viologen-phosphorus dendrimers induce no apoptosis or necrosis in the murine neuroblastoma cell line N2a, thereby commending these viologen dendrimers for use in in vivo trials in mice. [16] The biological investigations of viologen dendrimers have already been presented in a review. [17] By means of a micro cell and cyclic voltammetric measurements we can detect the time-dependent loss of dendrimer concen-tration in solution and investigate the influence of sodium chloride and ethidium bromide.…”

Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro

“…Orange acridine (OA) and ethidium bromide (EB) double staining was carried out [16]. Both dyes exhibit fluorescence after intercalation in DNA.…”

“…Sample resin blocks were sectioned on an Ultra Cut E (Reichert Jung, Germany) ultramicrotome with a glass knife. Ultrathin sections (60-70 nm) were placed on formvar coated nickel grids and stained with a uranyl acetate and lead citrate [16,17]. The cell ultrastructure was examined using a transmission electron microscope JEM 1010 (JEOL, Japan) at 80 kV.…”

The influence of heterocyclic compound-PAMAM dendrimer complexes on evoked electrical responses in slices of hypoxic brain tissue

“…Non-covalent or covalent conjugation with dendrimers can significantly improve the direct delivery of drugs, including anticancer drugs like adriamycin, doxorubicin, methotrexate, fluorouracil, or cisplatin [4,[6][7]. Moreover, modification with a dendrimer can greatly reduce the drug's side effects [8][9]. The aim of this study was to elucidate how the presence of dendrimerheterocyclic compound complexes in brain tissue would affect the functioning of its signaling systems under hypoxic conditions.…”