An Early Developmental Vertebrate Model for Nanomaterial Safety: Bridging Cell-Based and Mammalian Toxicity Assessment

Webster, Carl A; Silvio, Desirè Di; Devarajan, Aarthi R.; Bigini, Paolo; Micotti, Edoardo; Giudice, Chiara; Salmona, Mario; Wheeler, Grant N.; Sherwood, Victoria; Bombelli, Francesca Baldelli

doi:10.2217/nnm.15.219

Cited by 21 publications

(30 citation statements)

References 49 publications

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“…The biological behavior of nanoparticles (NPs) is currently receiving much attention, in particular to enhance our understanding of any potential hazards involved in NP exposure and to optimize the use of nanotechnology in biomedical applications [ 1 – 3 ]. Most studies to date involve the use of cell cultures as a good model system that can provide in-depth mechanistic insight into the precise nature of how the cells interact with the engineered NPs [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of nanoparticle-driven lysosomal alkalinization on cellular functionality

et al. 2018

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BackgroundThe biomedical use of nanosized materials is rapidly gaining interest, which drives the quest to elucidate the behavior of nanoparticles (NPs) in a biological environment. Apart from causing direct cell death, NPs can affect cellular wellbeing through a wide range of more subtle processes that are often overlooked. Here, we aimed to study the effect of two biomedically interesting NP types on cellular wellbeing.ResultsIn the present work, gold and SiO2 NPs of similar size and surface charge are used and their interactions with cultured cells is studied. Initial screening shows that at subcytotoxic conditions gold NPs induces cytoskeletal aberrations while SiO2 NPs do not. However, these transformations are only transient. In-depth investigation reveals that Au NPs reduce lysosomal activity by alkalinization of the lysosomal lumen. This leads to an accumulation of autophagosomes, resulting in a reduced cellular degradative capacity and less efficient clearance of damaged mitochondria. The autophagosome accumulation induces Rac and Cdc42 activity, and at a later stage activates RhoA. These transient cellular changes also affect cell functionality, where Au NP-labelled cells display significantly impeded cell migration and invasion.ConclusionsThese data highlight the importance of in-depth understanding of bio-nano interactions to elucidate how one biological parameter (impact on cellular degradation) can induce a cascade of different effects that may have significant implications on the further use of labeled cells.

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Section: Introductionmentioning

confidence: 99%

The impact of nanoparticle-driven lysosomal alkalinization on cellular functionality

et al. 2018

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“…Furthermore, it was shown that nanoparticle sizes above 200 nm had toxic effects. 21 Despite available literature on the effects of many Please do not adjust margins compounds on the larval development of X. laevis in environmental studies, there are only few reports evaluating nanoparticles toxicity and biodistribution designed for biomedical applications, 22,23 and there is still a lack of knowledge bridging biotransformation studies in cell-based assays with data generated from rodent in vivo systems.…”

Section: Introductionmentioning

confidence: 99%

Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in aXenopus laevismodel

et al. 2018

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Multicore superparamagnetic nanoparticles have been proposed as ideal tools for some biomedical applications because of their high magnetic moment per particle, high specific surface area and long term colloidal stability. Through controlled aggregation and packing of magnetic cores it is possible to obtain not only single-core but also multicore and hollow spheres with internal voids. In this work, we compare toxicological properties of single and multicore nanoparticles. Both types of particles showed moderate in vitro toxicity (MTT assay) tested in Hep G2 (human hepatocellular carcinoma) and Caco-2 (human colorectal adenocarcinoma) cells. The influence of surface chemistry in their biological behavior was also studied after functionalization with O,O'-bis(2-aminoethyl) PEG (2000 Da). For the first time, these nanoparticles were evaluated in a Xenopus laevis model studying their whole organism toxicity and their impact upon iron metabolism. The degree of activation of the metabolic pathway depends on the size and surface charge of the nanoparticles which determine their uptake. The results also highlight the potential of Xenopus laevis model bridging the gap between in vitro cell-based assays and rodent models for toxicity assessment to develop effective nanoparticles for biomedical applications.

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“…embryos represent a valuable model to bridge in vitro and in vivo studies using mammals, with negligible ethical implications. To confirm this, a study by Webster and collaborators (Webster et al 2016) showed that after exposure to a range of NPs, the phenotypic score of Xenopus embryos showed a strong correlation with in vitro cell tests and, in particular, magnetite cored NPs, negative for toxicity in vitro and Xenopus, were further confirmed as nontoxic in mice.…”

Section: Discussionmentioning

confidence: 92%

Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

et al. 2019

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Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe 3 O 4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification.

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An Early Developmental Vertebrate Model for Nanomaterial Safety: Bridging Cell-Based and Mammalian Toxicity Assessment

Abstract: The results highlight the potential of Xenopus embryo analysis as a fast screening approach for toxicity assessment of NPs, which could be introduced for the routine testing of nanomaterials.

Cited by 21 publications

References 49 publications

The impact of nanoparticle-driven lysosomal alkalinization on cellular functionality

The impact of nanoparticle-driven lysosomal alkalinization on cellular functionality

Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in aXenopus laevismodel

Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

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