Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies

Demokritou, P; Büchel, Robert; Molina, Ramon M.; DeLoid, Glen M.; Brain, Joseph D.; Pratsinis, Sotiris E.

doi:10.3109/08958378.2010.499385

Cited by 58 publications

(69 citation statements)

References 36 publications

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“…The Fe 2 O 3 material for this case study was made by Flame Spray Pyrolysis (FPS) using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES) 86 as described previously 42,86,87 .The powder characterization and colloidal characterization in DMEM + 10% (vol/vol) FBS for this material are presented in Table 4. The sonicator used was a Branson model S-450D with 3-inch I.D.…”

Section: Anticipated Resultsmentioning

confidence: 99%

“…no 544884, and TiO 2 , cat. no 637262), or produced industrially or in the lab by methods such as Flame Spray Pyrolysis (for example, as generated by the Harvard Versatile Engineered Nanomaterial Generation System (VENGES) 86 as described previously 42,86,87 , or generated during use or disposal of nano-enabled products and ambient nanoparticles collected from air samples 25,88 .…”

Section: Methodsmentioning

confidence: 99%

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Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

et al. 2017

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Summary Evidence continues to grow of the importance of in vitro and in vivo dosimetry in the hazard assessment and ranking of engineered nanomaterials (ENMs). Accurate dose metrics are particularly important for in vitro cellular screening to assess the potential health risks or bioactivity of ENMs. In order to ensure meaningful and reproducible quantification of in vitro dose, with consistent measurement and reporting between laboratories, it is necessary to adopt standardized and integrated methodologies for 1) generation of stable ENM suspensions in cell culture media, 2) colloidal characterization of suspended ENMs, particularly properties that determine particle kinetics in an in vitro system (size distribution and formed agglomerate effective density), and 3) robust numerical fate and transport modeling for accurate determination of ENM dose delivered to cells over the course of the in vitro exposure. Here we present such an integrated comprehensive protocol based on such a methodology for in vitro dosimetry, including detailed standardized procedures for each of these three critical steps. The entire protocol requires approximately 6-12 hours to complete.

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Section: Anticipated Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

et al. 2017

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“…The MMAD was 281 nm. It is worth noting that this is the only published study that used a truly nanoscale aerosol exposure atmosphere generated using an industry relevant flame spray pyrolysis system (Harvard VENGES system) 70 . BAL levels of neutrophils increased 6 fold 24 h post-exposure indicating inflammation, while BAL activity of LDH increased 2 fold indicating cytotoxicity.…”

Section: Pulmonary Deposition and Responsementioning

confidence: 99%

The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity

Yokel

Hussain

Garantziotis

et al. 2014

Environ. Sci.: Nano

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This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. Nanoceria reaching the blood is primarily distributed to mononuclear phagocytic system organs. Available data suggest nanoceria’s distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance rates. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce granuloma in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria’s biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distal to exposure may be due to nanoceria translocation or released biomolecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface Ce3+, which becomes more relevant as particle size decreases and the ratio of surface area to volume increases. Given its biopersistence and resulting increased toxicity with time, there is a risk that long-term exposure to low nanoceria levels may eventually lead to adverse health effects. This critical review provides recommendations for research to resolve some of the many unknowns of nanoceria’s fate and adverse effects.

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“…Chan School of Public Health Center for Nanotechnology and Nanotoxicology using the versatile engineered nanomaterial-generation system, as previously described. 29 The primary particle size was determined for Fe 2 O 3 and ZnO ENPs using X-ray diffraction. Prior to each experiment, the ENPs were suspended in sterile distilled injectable water at 5 mg/mL.…”

Section: Particle Reagentsmentioning

confidence: 99%

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

Watson¹,

Molina²,

Louzada³

et al. 2015

IJN

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Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65 ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa . Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65 ZnO ENPs. There was a time-dependent decrease in tissue levels of 65 Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P . aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

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Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies

Cited by 58 publications

References 36 publications

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

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