Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes

Frőhlich, Eleonore; Kueznik, Tatjana; Samberger, Claudia; Roblegg, Eva; Wrighton, Christopher J.; Pieber, Thomas R.

doi:10.1016/j.taap.2009.11.002

Cited by 106 publications

(76 citation statements)

References 25 publications

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“…In vitro experiments showed higher cytotoxicity of well-dispersed mesoporous silica and amorphous silica, dolomite, ZnO, Ni, Ag, and polystyrene NPs compared to the respective microparticles. [6][7][8][9][10][11][12][13][14][15] When particles smaller than 100 nm are compared, still-smaller particles act more toxically than larger ones (quantum dots, 16 TiO 2 17 ). In contrast to these studies, no differences have been reported for 10-100 nm silica particles compared to 45 µm ones, 18 and for nickel ferrite NPs.…”

Section: Cytotoxicitymentioning

confidence: 99%

“…Inside the cells, NPs may interfere with mitochondrial metabolism (6), causing generation of radicals and induction of apoptosis. Intracellular ROS generation by NPs or by metals from lysosomal degradation (7) as well as lysosomal disruption (8) and direct binding to components of the cytoskeleton (9) and the induction of structural alterations of proteins (10) are additional modes of toxic actions. In the nucleus, interference with the transcription machinery and oxidative damage of the DNA (11) …”

Section: Charge-dependent Cytotoxicitymentioning

confidence: 99%

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The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

Frőhlich¹

2012

IJN

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2,010

1,416

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Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.

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Section: Cytotoxicitymentioning

confidence: 99%

Section: Charge-dependent Cytotoxicitymentioning

confidence: 99%

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

Frőhlich¹

2012

IJN

Self Cite

2,010

1,416

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“…The TiO 2 P25-300 fraction was mainly composed of heavily agglomerated/aggregated particles, while TiO 2 P25-130 and TiO 2 P25-70 were composed of much smaller agglomerates/aggregates (Figure 1). The sub-100 nm fraction (ie, TiO 2 P25-70 ) was found to be stable without agglomeration and sedimentation for more than a week, whereas the TiO 2 P25-300 and TiO 2 P25-130 fractions were easily aggregated and sedimented in slight acidic conditions (pH [4][5] cause problems in performing accurate and reproducible toxicity assessments of nanoparticles. 5,[23][24][25][26][27] To overcome this problem of colloidal instability, nanoparticles are often stabilized with various surface-modifying ligands.…”

Section: P25-70mentioning

confidence: 99%

“…1,2 The size and surface area of materials are crucial characteristics from a toxicological perspective. [3][4][5] Because nanomaterials have an increased surface area compared with bulk materials, nanomaterials are expected to be more reactive and have more interaction with living organisms.…”

Section: Introductionmentioning

confidence: 99%

Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

Yoo¹,

Yoon²,

Kwon³

et al. 2012

IJN

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Background: Titanium dioxide (TiO 2 ) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO 2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO 2 has yet to be defined. Methods and results:In this study, we demonstrated that combined treatment with TiO 2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO 2 nanoparticles with a hydrodynamic size distribution centered around 70 nm ) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO 2 -induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO 2 P25-70 and ultraviolet A irradiation. Conclusion:These results indicate that sub-100 nm sized TiO 2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.

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“…Expressed CYP2C9 was slightly less inhibited (84%) (Sereemaspun et al, 2008). Nonmetallic carboxyl polystyrene particles (20 -60 nm) inhibited the enzymatic activity of several P450 enzymes (CYP3A4, CYP2D6, and CYP2C9) in both insect cell membrane preparations and liver microsomes (Fröhlich et al, 2010), suggesting that "inert" nanoparticles in and of themselves can produce unexpected effects on liver cell function. The present study sought to evaluate whether nanosilver particles also have the potential to affect important liver cell functions such as detoxification and elimination of drugs and, therefore, could be a potential source of unanticipated drug-drug interactions in the human population.…”

Section: Introductionmentioning

confidence: 99%

Nanosilver Particle Effects on Drug Metabolism In Vitro

Lamb¹,

Hathaway²,

Munger

et al. 2010

Drug Metab Dispos

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ABSTRACT:Nanosilver particles are present in consumer and health care products. Their effects on human microsomal cytochrome P450 (P450) activities and induction in luciferase reporter-engineered Caco-2 (MDR1.C) and HepG2 (DPX2 and 1A2DRE) cells have been investigated. The LD 50 values were ϳ4 g silver/ml for HepG2 and 5 g/ml for Caco-2 cells. At silver concentrations that showed no decreased cell viability (<1 g silver/ml), the pregnane X receptor (PXR)-driven 4.5-fold induction response of MDR1.C cells to 50 M omeprazole was unaffected. In DPX2 cells, the PXR-driven 5.5-and 6.5-fold induction responses to omeprazole and 10 M rifampicin were attenuated to 4-and 3.5-fold, respectively. Nanosilver particles alone showed no induction. In 1A2DRE cells, the aryl hydrocarbon receptor-driven 5.5-fold induction response to omeprazole was attenuated to 4-fold. In 1A2DRE cells, nanosilver alone elicited slight induction at 1 g/ml. The inhibition of human P450-selective activities by nanosilver particles in vitro was proportional to the silver/microsomal protein ratio. At a fixed (0.5 mg/ml) protein concentration, P450-selective activities differed in sensitivity (IC 50 value).

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Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes

Cited by 106 publications

References 25 publications

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

Nanosilver Particle Effects on Drug Metabolism In Vitro

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