A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

Kermanizadeh, Ali; Powell, Leagh; Stone, Vicki

doi:10.1080/10937404.2020.1751756

Cited by 39 publications

(31 citation statements)

References 171 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As materials scientists and engineers have mastered the art of designing and synthesizing distinctive nanomaterials, their utilization in everyday products and applications has grown exponentially. The rise of nanotechnology has proven to be a double-edged sword, however, as the same physicochemical properties that make these materials attractive for applications also make them a hazard to living biological systems [ 44 ]. As each unique NP set has the potential to elicit differential toxicological profiles, this has created the vast need to evaluate the health and safety of every particle type.…”

Section: Discussionmentioning

confidence: 99%

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

et al. 2021

View full text Add to dashboard Cite

The incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable challenge, as their reactivity and variable behavior have given rise to discrepancies between standard cell-based in vitro and animal in vivo models. In this study, enhanced in vitro models were generated that retained the advantages of traditional cell cultures, but incorporated the modifications of (1) inclusion of an activated immune element and (2) the presence of physiologically-relevant dynamic flow. Following verification that the human alveolar epithelial and macrophage (A549/U937) co-culture could be successfully sustained under both static and dynamic conditions, these cultures, in addition to a standard A549 static model, were challenged with 10 nm citrate coated silver NPs (AgNPs). This work identified a reshaping of the AgNP-cellular interface and differential biological responses following exposure. The presence of dynamic flow modified cellular morphology and reduced AgNP deposition by approximately 20% over the static exposure environments. Cellular toxicity and stress endpoints, including reactive oxygen species, heat shock protein 70, and secretion of pro-inflammatory cytokines, were found to vary as a function of both cellular composition and flow conditions; with activated macrophages and fluid flow both mitigating the severity of AgNP-dependent bioeffects. This work highlights the possibility of enhanced in vitro systems to assess the safety of engineered NPs and demonstrates their effectiveness in elucidating novel NP-cellular interactions and toxicological profiles.

show abstract

Section: Discussionmentioning

confidence: 99%

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although, most of the histopathological findings in the positive studies in Table 1 do not demonstrate a definitive, irreversible adverse outcome such as liver fibrosis (or any effects at all), these findings can potentially progress to liver fibrosis due to further prolonged exposure. However, the exact mechanism of hepatic toxicity caused by SAS is unknown and a topic of present research (Kermanizadeh, Powell, and Stone 2020;Medina-Reyes et al 2020;Murugadoss et al 2017;Qi et al 2020). Yet, as SAS is present in many everyday products, humans will be exposed to SAS on a daily basis over a prolonged period.…”

Section: Mode Of Actionmentioning

confidence: 99%

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure

et al. 2021

View full text Add to dashboard Cite

Synthetic amorphous silica (SAS) is applied in food products as food additive E 551. It consists of constituent amorphous silicon dioxide (SiO 2 ) nanoparticles that form aggregates and agglomerates. We reviewed recent oral toxicity studies with SAS. Some of those report tissue concentrations of silicon (Si). The results of those studies were compared with recently determined tissue concentrations of Si (and Si-particles) in human postmortem tissues. We noticed inconsistent results of the various toxicity studies regarding toxicity and reported tissue concentrations, which hamper the risk assessment of SAS. A broad range of Si concentrations is reported in control animals in toxicity studies. The Si concentrations found in human postmortem tissues fall within this range. On the other hand, the mean concentration found in human liver is higher than the reported concentrations causing liver effects in some animal toxicity studies after oral exposure to SAS. Also higher liver concentrations are observed in other, negative animal studies. Those inconsistencies could be caused by the presence of other Si-containing chemical substances or particles (which potentially also includes background SAS) and/or different sample preparation and analytical techniques that were used. Other factors which could explain the inconsistencies in outcome between the toxicity studies are the distinct SAS used and different dosing regimes, such as way of administration (dietary, via drinking water, oral gavage), dispersion of SAS and dose. More research is needed to address these issues and to perform a proper risk assessment for SAS in food. The current review will help to progress research on the toxicity of SAS and the associated risk assessment.

show abstract

“…However, retention in the liver or spleen can take up a long time depending on their size and surface chemistry. (Kermanizadeh et al 2020 ; Feliu et al 2016 ) These accumulations in the RES and the slow elimination, taking months or even years to clear the body, can be problematic for clinical translation. On the other hand, clearance through the kidneys occurs quickly, as the nanoparticles are filtered from the blood and excreted out.…”

Section: Introductionmentioning

confidence: 99%

Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization

et al. 2021

View full text Add to dashboard Cite

Background In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. Results Our ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS. Conclusion These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.

show abstract

A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

Cited by 39 publications

References 171 publications

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure

Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization

Contact Info

Product

Resources

About