Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Corbalan, J. Jose; Medina, Carlos; Jacoby, Adam; Maliński, Tadeusz; Radomski, Marek W.

doi:10.2147/ijn.s28293

Cited by 40 publications

(20 citation statements)

References 42 publications

(26 reference statements)

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“…As indicated by the supplier (Polysciences, Warrington, PA, USA), the commercially available negative surface-charged silica nanoparticles used in our studies were amorphous solid (nonporous) pure silicon dioxide synthesized by a precipitation process. Using the same type of SiNP from the same source, Corbalan et al [13,17] confirmed the size stated by the supplier and found that the zeta potential of the silica nanoparticles was more negative than -30 mV.…”

Section: Methodsmentioning

confidence: 70%

“…Their characteristics were recently studied [13,17]. As indicated by the supplier (Polysciences, Warrington, PA, USA), the commercially available negative surface-charged silica nanoparticles used in our studies were amorphous solid (nonporous) pure silicon dioxide synthesized by a precipitation process.…”

Section: Methodsmentioning

confidence: 99%

“…Exposure of human platelets in vitro to amorphous SiNP induces oxidative effects leading to platelet aggregation [13]. We recently showed that intraperitoneal administration of SiNP causes proinflammatory and procoagulant responses in vivo and in vitro [14].…”

Section: Introductionmentioning

confidence: 99%

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Interaction of Amorphous Silica Nanoparticles with Erythrocytesin Vitro: Role of Oxidative Stress

Nemmar¹,

Beegam²,

Yuvaraju³

et al. 2014

Cell Physiol Biochem

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Background/Aims: The use of engineered nanomaterials in the form of nanoparticles (NP) for various biomedical applications, as well as in consumer products, has raised concerns about their safety for human health. These NP are intended to be administered directly into the circulation following intravenous injection, or they may reach the circulation following other routes of administration such as oral or inhalation, and interact with circulating cells such as erythrocytes. However, little is known about the interaction of amorphous SiNP with erythrocytes. Methods: We studied the interaction of amorphous silica nanoparticles (SiNP) at various concentrations (1, 5, 25 and 125µg/ml) with mouse erythrocytes in vitro. Results: Incubation of erythrocytes with SiNP caused a dose-dependent hemolytic effect. Likewise, the activity of lactate dehydrogenase was dose-dependently increased by SiNP. Transmission electron microscopy analysis revealed that SiNP are taken up by erythrocytes. Lipid erythrocyte susceptibility to in vitro peroxidation measured by malondialdehyde showed a significant and dose-dependent increase in erythrocytes. SiNP also enhanced the antioxidant activities of superoxide dismutase (SOD), catalase and reduced glutathione (GSH). Moreover, SiNP increased caspase 3, triggered annexin V-binding and caused a dose-dependent increase of cytosolic calcium concentration. Conclusion: It can be concluded that SiNP cause a dose-dependent hemolytic activity and are taken up by the erythrocytes. We also found that SiNP induce the occurrence of oxidative activity, apoptosis and increase cytosolic Ca²⁺, which may explain their haemolytic activity. Our in vitro data suggest that SiNP may, plausibly, lead to anemia and circulatory disorders in vivo.

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Section: Methodsmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

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Interaction of Amorphous Silica Nanoparticles with Erythrocytesin Vitro: Role of Oxidative Stress

Nemmar¹,

Beegam²,

Yuvaraju³

et al. 2014

Cell Physiol Biochem

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“…Alternatively, since SD has already opened the BBB due to stress, smaller-sized NPs could penetrate deeper into the brain, leading to more stress and cellular damage [46][47][48]65]. Damage to circulating platelets by smaller-sized NPs could induce additional release of 5-HT that may reach brain tissues due to breakdown in the BBB, leading to higher brain 5-HT levels in NP-intoxicated SD groups [68][69][70]. That Ag NPs of same size as Cu NPs produce greater damage suggests that the inherent properties of NPs are also important in bringing about oxidative stress or cellular damage [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

Sharma

Mureșanu²,

Lafuente

et al. 2015

Mol Neurobiol

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Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier.

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“…Silica nanoparticles (SNPs) of different sizes were found to activate glycoprotein IIb/IIIa and to induce the expression of P-selectin in platelets [16]. Additionally, SNPs were found to induce pre-thrombotic states through surface-driven activation of the coagulation factor XII [17,18].…”

Section: Introductionmentioning

confidence: 99%

Identification of physicochemical properties that modulate nanoparticle aggregation in blood

Soddu¹,

Trinh²,

Dunne³

et al. 2020

Beilstein J. Nanotechnol.

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Inorganic materials are receiving significant interest in medicine given their usefulness for therapeutic applications such as targeted drug delivery, active pharmaceutical carriers and medical imaging. However, poor knowledge of the side effects related to their use is an obstacle to clinical translation. For the development of molecular drugs, the concept of safe-by-design has become an efficient pharmaceutical strategy with the aim of reducing costs, which can also accelerate the translation into the market. In the case of materials, the application these approaches is hampered by poor knowledge of how the physical and chemical properties of the material trigger the biological response. Hemocompatibility is a crucial aspect to take into consideration for those materials that are intended for medical applications. The formation of nanoparticle agglomerates can cause severe side effects that may induce occlusion of blood vessels and thrombotic events. Additionally, nanoparticles can interfere with the coagulation cascade causing both pro- and anti-coagulant properties. There is contrasting evidence on how the physicochemical properties of the material modulate these effects. In this work, we developed two sets of tailored carbon and silica nanoparticles with three different diameters in the 100–500 nm range with the purpose of investigating the role of surface curvature and chemistry on platelet aggregation, activation and adhesion. Substantial differences were found in the composition of the protein corona depending on the chemical nature of the nanoparticles, while the surface curvature was found to play a minor role. On the other hand, large carbon nanoparticles (but not small carbon nanoparticles or silica nanoparticles) have a clear tendency to form aggregates both in plasma and blood. This effect was observed both in the presence or absence of platelets and was independent of platelet activation. Overall, the results presented herein suggest the existence of independent modes of action that are differently affected by the physicochemical properties of the materials, potentially leading to vessel occlusion and/or formation of thrombi in vivo.

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Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Cited by 40 publications

References 42 publications

Interaction of Amorphous Silica Nanoparticles with Erythrocytesin Vitro: Role of Oxidative Stress

Interaction of Amorphous Silica Nanoparticles with Erythrocytesin Vitro: Role of Oxidative Stress

Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

Identification of physicochemical properties that modulate nanoparticle aggregation in blood

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