Silver nanoparticles exposure induces developmental neurotoxicity in hiPSC-derived cerebral organoids

Huang, Yan; Guo, Lulu; Cao, Chulin; Ma, Rui; Huang, Yu-Ting; Gao, Hong; Huang, Yina; Bu, Qian

doi:10.1016/j.scitotenv.2022.157047

Cited by 25 publications

(10 citation statements)

References 48 publications

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“…Human iPSC-derived neurons-based 3D brain organoids containing a variety of neurons and glial cells possess a more complete organization and are more similar to the human central nervous system [ 57 ]. The toxic effects of silver nanoparticles [ 58 ] and zinc oxide nanoparticles [ 59 ] have been investigated using brain organoids. Researchers also use MEA [ 60 ] and whole-cell patch-clamp [ 61 ] to record brain organoids’ electrophysiological response to external stimulation.…”

Section: Discussionmentioning

confidence: 99%

The cytological and electrophysiological effects of silver nanoparticles on neuron-like PC12 cells

et al. 2022

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The aim of this study was to investigate the toxic effects and mechanism of silver nanoparticles (SNPs) on the cytological and electrophysiological properties of rat adrenal pheochromocytoma (PC12) cells. Different concentrations of SNPs (20 nm) were prepared, and the effects of different application durations on the cell viability and electrical excitability of PC12 quasi-neuronal networks were investigated. The effects of 200 μM SNPs on the neurite length, cell membrane potential (CMP) difference, intracellular Ca2+ content, mitochondrial membrane potential (MMP) difference, adenosine triphosphate (ATP) content, and reactive oxygen species (ROS) content of networks were then investigated. The results showed that 200 μM SNPs produced grade 1 cytotoxicity at 48 h of interaction, and the other concentrations of SNPs were noncytotoxic. Noncytotoxic 5 μM SNPs significantly increased electrical excitability, and noncytotoxic 100 μM SNPs led to an initial increase followed by a significant decrease in electrical excitability. Cytotoxic SNPs (200 μM) significantly decreased electrical excitability. SNPs (200 μM) led to decreases in neurite length, MMP difference and ATP content and increases in CMP difference and intracellular Ca2+ and ROS levels. The results revealed that not only cell viability but also electrophysiological properties should be considered when evaluating nanoparticle-induced neurotoxicity. The SNP-induced cytotoxicity mainly originated from its effects on ATP content, cytoskeletal structure and ROS content. The decrease in electrical excitability was mainly due to the decrease in ATP content. ATP content may thus be an important indicator of both cell viability and electrical excitability in PC12 quasi-neuronal networks.

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Section: Discussionmentioning

confidence: 99%

The cytological and electrophysiological effects of silver nanoparticles on neuron-like PC12 cells

et al. 2022

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“…On the other hand, exposure to AgNPs at high concentration reduced cell proliferation and allowed apoptosis in cerebral organoids, modeling neurotoxicity at both low and high concentrations that consequently causes abnormal neural development. [49] Human embryonic stem cells (hESCs) have also been developed into cerebral organoids that may resemble an early human cerebral cortex. [15] In Dang et al study, Zika virus has shown its effect in decreasing hESC-derived organoid size through activation of Toll-Like-Receptor 3 (TLR3).…”

Section: Matrigelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Development of Brain Organoids for Biomedical Application

Kim

Jang

Sankpal

et al. 2022

Macromolecular Bioscience

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Over the years, scientists have studied the behavior and anatomy of many animals to understand the own species. However, despite the continuous efforts, it is often difficult to know for certain how the brain works due to the differences between the brains of animals and the human brain. While the use of animal models for research continues, the origin of human cognition and neurological disorders needs further elucidation. To that end, in vitro organoids that exhibit in vivo characteristics of the human brain have been recently developed. These brain-like organoids enable researchers to dive deeper into understanding the human brain, its neurological structures, and the causes of neurological pathologies. This paper reviews the recent developments in the regeneration of brain-like organoids using Matrigel and other alternatives. Further, gel-free methods that may enhance the regeneration process of organoids are discussed. Finally, the vascularized brain organoid growth and development in both in vitro and in vivo conditions are detailed.

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“…Recently, several studies have shown the potential of organoids as a physiologically relevant model to assess nanomaterial toxicity. − Huang et al reported the toxicity of silver nanoparticles using cerebral organoids, and Park et al established a toxicity assessment of nanoparticles using colon organoids . Although these studies shed light on the potential of organoids as a tool for assessing nanoparticle toxicity, limitations still exist.…”

mentioning

confidence: 99%

“…One major limitation is the lack of confirmation of nanoparticle internalization in cells within organoids. Despite these studies reporting the toxicity of nanoparticles in organoid systems, these studies do not provide direct evidence of nanoparticle internalization and subcellular localization. − This lack of confirmation raises concerns regarding the reliability and validity of the reported toxicological outcomes.…”

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confidence: 99%

Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials

Baek,

Kwon,

Lee

et al. 2024

Nano Lett.

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Over the past few decades, the increased application of nanomaterials has raised questions regarding their safety and possible toxic effects. Organoids have been suggested as promising tools, offering efficient assays for nanomaterial-induced toxicity evaluation. However, organoid systems have some limitations, such as size heterogeneity and poor penetration of nanoparticles because of the extracellular matrix, which is necessary for organoid culture.Here, we developed a novel system for the improved safety assessment of nanomaterials by establishing a 3D floating organoid paradigm. In addition to overcoming the limitations of twodimensional systems including the lack of in vitro−in vivo crosstalk, our method provides multiple benefits as compared with conventional organoid systems that rely on an extracellular matrix for culture. Organoids cultured using our method exhibited relatively uniform sizing and structural integrity and were more conducive to the internalization of nanoparticles. Our floating culture system will accelerate the research and development of safe nanomaterials.

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Silver nanoparticles exposure induces developmental neurotoxicity in hiPSC-derived cerebral organoids

Cited by 25 publications

References 48 publications

The cytological and electrophysiological effects of silver nanoparticles on neuron-like PC12 cells

The cytological and electrophysiological effects of silver nanoparticles on neuron-like PC12 cells

Recent Development of Brain Organoids for Biomedical Application

Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials

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