Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles

Khan, Mohammad Imran; Mohammad, Akbar; Patil, Govil; Naqvi, Saba; Chauhan, Lalit Kumar Singh; Ahmad, Iqbal

doi:10.1016/j.biomaterials.2011.10.080

Cited by 438 publications

(314 citation statements)

References 52 publications

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“…30,31 However, our results are in contrast to other studies that show IONP-induced ROS production. [32][33][34][35] Possible explanations for the discrepancies include one or more of the following factors: different types and sizes of IONPs used; different surface properties (eg, surface coatings) of the IONPs that affect the degradation potential and thus the exposure to the naked iron oxide core and the liberation of iron ions that might induce ROS; 32 different cell types used; higher IONP concentration; different (mostly longer) incubation times after which ROS production was measured and/or different methods for assessing intracellular ROS.…”

Section: Discussionmentioning

confidence: 99%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood.

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Section: Discussionmentioning

confidence: 99%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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“…The cellular amount of autophagosomes upon exposure to gold NPs, iron oxide NPs, fullerenes, carbon nanotubes, and quantum dots was increased due to oxidative stress, disruption of cytoskeleton, and mitochondrial damage. [76][77][78][79] In the absence of metals, either as an integrative part of the particles or as contamination, accumulation of autophagosomes has only been reported in cells exposed to NPs with positive surface charge, cationic polymeric NPs, polyplexes, and cationic dendrimers, and not for anionic NPs.…”

Section: Lysosomesmentioning

confidence: 99%

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

Frőhlich¹

2012

IJN

1,978

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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“…They also demonstrated that autophagy was the main reason of cytotoxicity. Similarly, Khan et al [67] found that iron oxide nanoparticles selectively elicited autophagic cell death in cancer cells (A549) but not in normal cells (IMR-90). In this case, autophagy was related with ROS production as well as mitochondrial damage.…”

Section: Iron-related Nanomaterialsmentioning

confidence: 87%

“…This is called "double-edged sword" effect of autophagy [27,30]. Therefore, it is crucial to take autophagy into consider in the study of biological effects of nanomaterials, since they may cause uncovered damage to organism through interfering with autophagic process [31]. On the other hand, it also implies that nanomaterials have the potential to be utilized in combination with chemotherapies for the treatment of diseases.…”

Section: Autophagymentioning

confidence: 99%

Autophagy as new emerging cellular effect of nanomaterials

et al. 2013

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The biosafety issue of nanoscale materials is getting more and more attention with their increasing manufacture and application. In the research of cellular effects and underlying mechanisms related to toxicity of nanomaterials, most emphasis were placed on processes such as apoptosis, metabolic inhibition and oxidative stress. Recent evidence suggests that autophagy is part of the biological effects by nanomaterials and various kinds of nanomaterials are capable of disturbing the autophagic process. This review will highlight the importance of autophagy as an emerging mechanism of nanomaterial toxicity and the implication in the therapy of autophagy-related diseases. We summarize current research status of interaction between nanomaterials and autophagic pathways. It is of note that nanomaterials can either induce or block autophagy, which result in similar phenotype but completely different biological consequence. It is therefore important to perform comprehensive analysis of the whole autophagic flux in the future research. Nanomaterials refer to materials with the size range between 1 and 100 nanometers in one or more dimensions [1]. Due to their superior physicochemical properties, such as ultra small size, increased ratio of surface area to volume, multiple options for modification and relatively good biocompatibilities, application of nanomaterials in research as well as in industry becomes more and more common. It is predicted that the total amount of nanomaterials' production will increase up to 58000 tons by 2020. Particularly, the utilization of nanomaterials in biomedical research as biosensors, drug-carriers, or imaging agents was extensively studied [2][3][4]. Large scaled preparation and application of nanomaterials increase their possibilities to be exposed to human beings or enter the environment [5][6][7]. Therefore the impact of nanomaterials on environment and human health has attracted high attention. Related studies were carried out on the biological effect of various kinds of nanomaterials both in vitro and in vivo [8]. To date, reported physiological changes of a cell or an organism that exposed to nanomaterials include: reactive oxygen species (ROS)-related pathological responses (such as damaged membrane, mitochondrial damage and necrosis), apoptosis, inflammation and altered differentiation patterns, etc [9][10][11][12]. Recently, autophagy as an essential cellular process and a novel biological effect of nanomaterials on eukaryotes, has received much attention. Many nanomaterials were reported to be able to change the basal level of autophagy [13,14]. Autophagy can crosstalk with other cellular process, such as apoptosis and necrosis, and therefore is an important part of the cellular effect of nanomaterials [15,16]. Moreover, nanomaterials-induced autophagy showed potential for the treatment of certain diseases including neurodegenerative diseases and cancer [13,17]. Hence, in this review we summarize the current research on the effect of various kinds of nanomaterials on autophagy. ...

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Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles

Cited by 438 publications

References 52 publications

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

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

Autophagy as new emerging cellular effect of nanomaterials

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