Distinct autophagy-inducing abilities of similar-sized nanoparticles in cell culture and live<i>C. elegans</i>

Wang, Qin; Zhou, Yanfeng; Fu, Rong; Zhu, Yi; Song, Bin; Zhong, Yiling; Wu, Sicong; Shi, Yu; Wu, Yanling; Su, Yuanyuan; Zhang, Huimin; He, Yao

doi:10.1039/c8nr05851b

Cited by 9 publications

(8 citation statements)

References 69 publications

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“…Caenorhabditis elegans (C. elegans) is a well-established small nematode model organism that has been used since the 1970s [63]. Unlike the traditional toxicity cell culture testing systems, C. elegans provide data from a whole animal with complete and metabolically active digestive, reproductive, endocrine, sensory, and neuromuscular systems [64]. Indeed, C. elegans research has been proved to be essential in the clarification of several basic aspects of biology, including apoptosis, autophagy, RNA interference, and miRNA function.…”

Section: Elegans Modelmentioning

confidence: 99%

“…Regarding the nanomaterial-induced autophagy, C. elegans has been employed to identify and characterize the autophagy-regulating mechanism, and 139 conserved genes that regulate autophagy activity are identified, offering a framework for thorough dissection of the autophagy process [68]. Studies show that treatment of quantum dots (QDs), gold nanoparticles (AuNPs), and carbon dots (CDs) are able to induce massive autophagosome formation, autophagy related gene upregulation, and autophagy substrate degradation in cultured HeLa cells and in live C. elegans [64]. Due to the small size of C. elegans, it is very easy to track the autophagosome formation in real-time by simply using the fluorescence microscopy [69], making C. elegans a suitable model organism for the alternative nanotoxicity approach and providing great connection between in vitro and in vivo toxicity [69].…”

Section: Elegans Modelmentioning

confidence: 99%

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The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

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Section: Elegans Modelmentioning

confidence: 99%

Section: Elegans Modelmentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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“…And p62 interacts with LC3 and degrades during the fusion of autophagosomes and lysosomes, so there is a inverse correlation between the expression of p62 and autophagy activity (Ji et al, 2016). Autophagy and the whole process of autophagy flux should be monitored by combining multiple methods, such as TEM, LC3 and p62 expression in protein and gene level, rather than just one index (Wang et al, 2018).…”

Section: Main Mechanisms Of Cytotoxicity Induced By Three Kinds Of Qdsmentioning

confidence: 99%

Research advance on cell imaging and cytotoxicity of different types of quantum Dots

Huang

Tang

2020

J of Applied Toxicology

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Quantum dots (QDs), as one of the emerging nanomaterials, have been widely studied by scientists due to their advantages and potential in bioimaging, especially cell imaging. Cadmium (Cd)‐based QDs, which have the best photoluminescence property, have received widespread attention. However, due to the obvious toxicity problem of these QDs, their cell imaging application is hindered. Recently, the emergence of Cd‐free‐metal and metal‐free QDs with lower toxicity makes people consider that Cd‐based QDs may be substituted by these QDs. However, problems of these QDs in cytotoxicity also cannot be ignored. Some reports claimed that their prepared emerging QDs for cell imaging were low toxicity, but there still exist up‐regulation of oxidative stress, inflammation, and apoptosis from other reports. And, up to now, few reports have separately summarized and discussed the issues of cell imaging and cytotoxicity of different types of QDs. Therefore, in this review, we classify QDs as following three types, Cd‐based, Cd‐free‐metal and metal‐free QDs, focus on the cell, the essential unit of life, discuss cell imaging application and cytotoxicity of QDs, and finally elucidate main mechanisms of cytotoxicity respectively. This review provides reference for the toxicity evaluation of QDs and highlights the potential cytotoxicity of Cd‐free QDs.

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“…They used four types of similar sized nanomaterials including silicon nanoparticles (SiNP), CdTe quantum dots, carbon dots, and AuNPs. They observed that unlike other nanomaterials tested, no autophagosome formation was detected in C. elegans with SiNP exposure, suggesting that the "nanoscale" size is not the determining factor for the nanomaterials to induce autophagy in C. elegans [41]. A recent microarray study showed that developmental changes in C. elegans following mercaptoundecanoic acid-coated AuNPs were related to differential gene expression in clec-174 (involved in cellular defense), cut-3 and fil-1 (both involved in body morphogenesis), dpy-14 (expressed in embryonic neurons), and mtl-1 (functions in metal detoxification and homeostasis) genes [42].…”

Section: Discussionmentioning

confidence: 97%

“…The cellular uptake and toxicity of nanoparticles mainly depend on their size, shape, and surface chemistry [38][39][40]. Wang et al [41] used the C. elegans model to understand whether the "nanoscale" size is the determining factor for the nanomaterials to induce autophagy. They used four types of similar sized nanomaterials including silicon nanoparticles (SiNP), CdTe quantum dots, carbon dots, and AuNPs.…”

Section: Discussionmentioning

confidence: 99%

Reproductive Toxicity of Pomegranate Peel Extract Synthesized Gold Nanoparticles: A Multigeneration Study in C. elegans

Patel

Siddiqi

Sharma

et al. 2019

Journal of Nanomaterials

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C. elegans is a preferential model for testing environmental toxicity of compounds including nanomaterials. The impact of multigeneration exposure of gold nanoparticles (AuNPs) on the lifespan and fertility of C. elegans is not known and therefore is investigated in this study. We used pomegranate (Punica granatum) peel extracts as a reducing agent to synthesize gold nanoparticles (PPE-AuNPs) from chloroauric acid. Nematodes were grown till adult stage and then exposed to 25, 50, and 100 μg/ml of PPE-AuNPs at 20°C for 72 hours and then assessed for lifespan and fertility. The same protocols were followed for subsequent F1, F2, and F3 generations. The results showed that PPE-AuNPs dose-dependently but insignificantly reduced the lifespan of C. elegans. Exposure of PPE-AuNPs significantly and dose-dependently reduced the fertility of C. elegans in terms of the number of eggs produced. The reproductive toxicity of PPE-AuNPs was found to be minimal in parental generation (F0) and maximal in F3 generation. In conclusion, biologically synthesized PPE-AuNPs adversely affect the fertility of C. elegans while the factors responsible for reproductive toxicity are inherited by subsequent generations.

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Distinct autophagy-inducing abilities of similar-sized nanoparticles in cell culture and liveC. elegans

Abstract: Silicon nanoparticles, having the same size as the autophagy-inducing QDs, CDs and AuNPs, do not induce autophagy in vitro and in vivo.

Cited by 9 publications

References 69 publications

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Research advance on cell imaging and cytotoxicity of different types of quantum Dots

Reproductive Toxicity of Pomegranate Peel Extract Synthesized Gold Nanoparticles: A Multigeneration Study in C. elegans

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