Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups reveals negligible toxicity against three rodent cell-lines

Janaszewska, Anna; Ciolkowski, Michal; Wrobel, Dominika; Petersen, Johannes F.; Ficker, Mario; Christensen, Jørn B.; Bryszewska, Maria; Klajnert, Barbara

doi:10.1016/j.nano.2013.01.010

Cited by 59 publications

(48 citation statements)

References 16 publications

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“…Differences in toxicity have been observed for PAMAM dendrimers functionalised with hydrophobic [61,64], PEG [51,52], \ \OH [68] and pyrrolidine [66] terminal groups. In 2012, Albertazzi et al investigated the effect of hydrophobic chain functionalisation on the cytotoxicity of G4 PAMAM dendrimers interacting with primary neuronal cultures and the central nervous system (CNS) of animals [61].…”

Section: Cytotoxicity Of Pamam Dendrimersmentioning

confidence: 99%

PAMAM dendrimer - cell membrane interactions

Fox

Richardson

Briscoe

2018

Advances in Colloid and Interface Science

191

135

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. 2018 PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been hindered by uncertainties in their cytotoxicity, which is influenced by dendrimer generation (i.e. size and surface group density), surface chemistry, and dosage, as well as cell specificity. In this review, biomedical applications of polyamidoamine (PAMAM) dendrimers and some related cytotoxicity studies are first outlined. Alongside these in vitro experiments, lipid membranes such as supported lipid bilayers (SLBs), liposomes, and Langmuir monolayers have been used as cell membrane models to study PAMAM dendrimer-membrane interactions. Related experimental and theoretical studies are summarized, and the physical insights from these studies are discussed to shed light on the fundamental understanding of PAMAM dendrimer-cell membrane interactions. We conclude with a summary of some questions that call for further investigations.a b s t r a c t a r t i c l e i n f o Available online 27 June

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Section: Cytotoxicity Of Pamam Dendrimersmentioning

confidence: 99%

PAMAM dendrimer - cell membrane interactions

Fox

Richardson

Briscoe

2018

Advances in Colloid and Interface Science

191

135

View full text Add to dashboard Cite

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“…The assay is based on the reduction of MTT by cellular reductases of viable cells to a blue formazan product, the absorbance of which can be measured spectrophotometrically after solubilization [32]. The assay was performed as previously described [33]. Cells were seeded in 96-well microplates at a density of 1.5 × 10 4 cells/well in DMEM medium and incubated for 20 h. After 24 h dendrimer treatment, 0.5 mg/ml MTT was added to each well and incubated for 3 h. After this time, the MTT solution was discarded, DMSO was added to each well to dissolve the formazan crystals and the absorbance was measured at 570 nm using a microplate spectrophotometer (BioTek).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

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

Łaźniewska

Miłowska

Katir

et al. 2013

Cellular and Molecular Biology Letters

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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.

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“…Among these cell lines, immortalized embryonic mouse hippocampal cells (mHippoE-18) have been exposed to various concentrations of the dendrimer and evaluated for cell viability, mitochondrial membrane potential, and reactive oxygen species (ROS) formation, as well as their susceptibility to necrosis or apoptosis. 1 Despite the fact that the authors clearly demonstrate a significantly lower cytotoxicity observed following mHippoE-18 treatment with the PAMAM-pyrrolidone dendrimer as compared to that following administration of the unmodified PAMAM dendrimer, their statement that the former exerts "minor cytotoxicity" 1 upon the specific cell line is, in our opinion, not justified by either their data or the methodological approach followed.…”

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confidence: 90%

“…Their data demonstrate a dose-dependent neurotoxic effect of the PAMAM-pyrrolidone dendrimer throughout the concentration spectrum (in most cases, viability seems to be diminished by N 20% compared to control) and it should be noted that the experiments are performed in the presence of foetal bovine serum (FBS). 1 This means that the toxic effect of the dendrimer is demonstrated by Janaszewska et al 1 for a proliferating cell line and not under conditions representing a stable (non-proliferating) neuronal population. We should bear in mind that FBS affects dendrimer bioavailability, and stimulates cells to proliferate and compensate for any losses occurring due to dendrimer-induced toxicity.…”

mentioning

confidence: 96%

“…The authors 1 are certainly aware of this advantage of the mHippoE-18 cells as they have (to some extent) assessed cytomorphological changes through flowcytometry and fluorescence/phase-contrast microscopy in their studies. 1,9,10 However, the fact that all their experiments were conducted on a cytodynamically-active (proliferating) cell line, one can safely assume that their assessments underestimate the potential in vivo neurotoxicity of the dendrimers.…”

mentioning

confidence: 99%

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