Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction

Lee, Jong-Ho; Eun, Kyung; Kim, Min Soo; Hong, Hye Won; Chung, Dong June; Ryu, Gyu Ha; Myung, Heejoon

doi:10.1016/j.toxlet.2009.07.018

Cited by 102 publications

(66 citation statements)

References 19 publications

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“…A decrease in MitoTracker Orange fluorescence was also reported in HaCaT cells after PAMAM treatment [43]. It has been demonstrated that depolarization of the mitochondrial membrane occurred after cell treatment with PAMAM and this process was associated with apoptotic cell death [42,45], while PPI increased (G2) or caused fluctuations (G3) in ΔΨm [40]. Our studies showed that 24 h exposure of N2a to VPD with phosphonate surface groups led to a small depolarization of the mitochondrial membrane (Fig.…”

Section: Discussionsupporting

confidence: 74%

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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Section: Discussionsupporting

confidence: 74%

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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“…13,14 The oxidative stress leads to a release of inflammatory factors 15,16,17,18,19,20,reviewed by 21 and potential activation of apoptotic pathways. 22,23,24,25 It is also important to consider processes such as endosomal rupture (endosomolysis), 9,14 which can enhance the toxic response as released nanoparticles have been shown to localise in and subsequently damage organelles such as the mitochondria. 15,16 If medical applications are to remain a viable option for nanomaterials, then it will be essential to explore and better define the mechanisms involved in the toxic response.…”

mentioning

confidence: 99%

“…38 It has also been proposed that larger generation dendrimer nanoparticles and/or doses can cause the endosome to rupture (endosomolysis), via the so-called proton pump mechanism. 39,40,41 Supported by the fact that after ~16hrs the PAMAM dendrimers have been seen to be located in the mitochondria, 22,38 whereupon the oxidative stress is further increased, resulting in further MMPD, which can culminate in apoptosis. A similar inflammatory cascade has been reported in murine macrophages, although the evolution of the responses was observed to be somewhat slower.…”

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confidence: 99%

Numerical simulations of in vitro nanoparticle toxicity – The case of poly(amido amine) dendrimers

Maher¹,

Naha²,

Mukherjee³

et al. 2014

Toxicology in Vitro

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A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations. The model serves as a tool to interpolate and visualise the range of dose and temporal dependences and elucidate the mechanisms underlying the in vitro cytotoxic response to nanoparticle exposure and describes the interaction in terms of independent nanoparticle properties and cellular parameters, based on reaction rates. Such an approach could be a valid alternative to that of effective concentrations for classification of nanotoxicity and may lay the foundation for future quantitative structure activity relationships and predictive nanotoxicity models.3

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“…Some results suggest that full generations of PAMAM dendrimers are endocytosed into the cells through a lysosomal pathway, leading to lysosomal alkalinization and induction of mitochondriamediated apoptosis [11]. Other experimental data also prove the detrimental modulatory effects of cationic dendrimres (especially G4 and higher) on mitochondria function [12][13][14]. Nevertheless, there are only few literature data concerning the negative influence of half-generations of PAMAMs on mitochondria.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Seasonal Fluctuations on Rat Liver Mitochondria Response to Tested Compounds— A Comparison between Autumn and Spring. New Insight into Collecting and Interpretation of Experimental Data Originating from Different Seasons

Łabieniec-Watała¹,

Siewiera²

2013

CellBio

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Seasonal variations play an essential role in the metabolism, behavior and activity of the laboratory animals. This study was aimed to examine whether mitochondrial function can be influenced by the seasonal changes and how large is the impact of these fluctuations on experiments with using animal models and further results interpretation. Liver mitochondria were isolated from male Wistar rats and exposed to calcium ions, PAMAM dendrimers G2.5 or their combination: (Ca 2+ ) and dendrimer. The scientific hypothesis assumed that dendrimer G2.5 is able to limit the detrimental effect of Ca 2+ ions on mitochondria function, possibly through affecting the following parameters: calcium transport, mitochondrial potential and membrane fluidity. The activity of mitochondria was monitored using fluorescent labels. The changes in calcium transport were detected using Calcium Green 5-N, the mitochondrial membrane potential and membrane fluidity were elucidated using JC-1 and DPH, respectively. The experiments were carried out during the autumn (October/November) or during the spring (May/June). The obtained data emphasize the effect of seasonal differences on liver mitochondria originating from laboratory animals and outline the importance of planning the experiments during the same seasonal period in order to receive objective and reliable results in the future. Finally, it was revealed the neutral effect of G2.5 dendrimer on mitochondria and its inability to protect mitochondria against overload of calcium ions regardless of seasonality. It was also evidenced that liver mitochondria isolated from autumn-derived animals were more sensitive to calcium and/or dendrimer exposure in comparison with mitochondria isolated from animals investigated during the spring.

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Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction

Cited by 102 publications

References 19 publications

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

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

Numerical simulations of in vitro nanoparticle toxicity – The case of poly(amido amine) dendrimers

The Impact of Seasonal Fluctuations on Rat Liver Mitochondria Response to Tested Compounds— A Comparison between Autumn and Spring. New Insight into Collecting and Interpretation of Experimental Data Originating from Different Seasons

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