Elucidating the mechanism of the surface functionalization dependent neurotoxicity of graphene family nanomaterials

Guo, Zhiling; Zhang, Peng; Chetwynd, Andrew J.; Xie, Heidi Qunhui; Valsami-Jones, Eugénia; Zhao, Bin; Lynch, Iseult

doi:10.1039/d0nr04179c

Cited by 25 publications

(13 citation statements)

References 25 publications

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“…Our results exclusively showed that hydroxylation endows the GQDs with higher phytotoxicity than the other two functionalizations, with the lowest phytotoxicity arising from the aminated GQDs. Although there is no data in plant systems available for a comparison with our data, our results agree with some previous studies using cell lines, [18] bacteria [19] and fish [20] that aminated graphene or GQDs usually have lower toxicity than carboxylated and hydroxylated ones. Our data showed that surface functionalization dependent toxicity was not only observed for phenotypical data such as seedling length and biomass, but also for physiological response including impairment of photosynthesis and triggering of antioxidant defence and phytohormone regulation.…”

Section: Discussionsupporting

confidence: 92%

“…[ 33 ] Similarly, hydroxylated graphene showed higher acute neurotoxicity on human neuroblastoma cells than carboxylated and aminated graphene; however, the study also showed that aminated graphene caused more persistent toxicity than the other two functionalization. [ 18 ] These results indicate that longer‐term study may be necessary in the future. In addition, a recent study showed that 1–10 mg L −1 GQDs caused persistent toxicity to the photosynthesis of green algae ( Chlorella vulgaris ) which play a vital role in maintaining the food web in aquatic systems.…”

Section: Discussionmentioning

confidence: 99%

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Stress Response and Nutrient Homeostasis in Lettuce (Lactuca sativa) Exposed to Graphene Quantum Dots Are Modulated by Particle Surface Functionalization

Zhang

Guo

et al. 2021

Advanced Biology

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A 5‐d germination assay and a 14‐d hydroponic trial are performed to evaluate the impacts of graphene quantum dots (GQDs) on lettuce. Results show that GQDs are toxic to lettuce plants and that the effects are highly dependent on particle surface functionalization and plant growth stage. The germination rate is not affected by aminated GQDs (N‐GQDs) and carboxylated GQDs (C‐GQDs) but is reduced by hydroxylated GQDs (O‐GQDs) by 39–71%. During the hydroponic trial, N‐GQDs (50 mg L−1) increase the root dry weight by 34%, while C‐GQDs and O‐GQDs reduce it by 39% and 43%, respectively. Shoot dry weight is not affected by N‐GQDs but is reduced by C‐GQDs (44%) and O‐GQDs (36–55%) treatments. C‐GQDs and O‐GQDs cause oxidative damage, disruption of mineral and organic nutrients homeostasis, impairment of photosynthesis, and modulates the levels of phytohormones. Light‐triggered reactive oxygen species generation and oxidation of antioxidants in plants are the critical reason for the phytotoxicity and explain the difference between the different functionalizations. These findings suggest that GQDs may not be as safe as expected. Future studies should consider the modulation of surface chemistry to achieve optimal safety of GQDs, and more plant species should be tested over a longer‐term scale.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Stress Response and Nutrient Homeostasis in Lettuce (Lactuca sativa) Exposed to Graphene Quantum Dots Are Modulated by Particle Surface Functionalization

Zhang

Guo

et al. 2021

Advanced Biology

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“…More than a few decades have passed since the application of nanomaterials (NMs) in medicine and since the concept of nanotoxicity was formulated ( 1 ). Despite the time lapsed, concerns regarding their potential neurotoxicity ( 2 ) have yet to be fully addressed, primarily because of challenges in characterization resulting from their unique physicochemical properties. Recent studies found NMs (e.g., ZnO and magnetite NMs) can accumulate in the brain with distinct morphologies and forms that differ from their pristine counterpart, which can affect the cholinergic neurotransmission and thus brain health ( 3 , 4 ).…”

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confidence: 99%

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model

Guo

Zhang

Chakraborty

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the potential of nanomaterials (NMs) to cross the blood–brain barrier (BBB), as a function of their physicochemical properties and subsequent behavior, fate, and adverse effect beyond that point, is vital for evaluating the neurological effects arising from their unintentional entry into the brain, which is yet to be fully explored. This is not only due to the complex nature of the brain but also the existing analytical limitations for characterization and quantification of NMs in the complex brain environment. By using a fit-for-purpose analytical workflow and an in vitro BBB model, we show that the physiochemical properties of metallic NMs influence their biotransformation in biological matrices, which in turn modulates the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, their neurotoxicity. The data presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs.

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“…The sample was redissolved in 100 µl of acetonitrile/water (1:1, v/v), adequately vortexed, and then centrifuged (18,800 g , 4°C, 15 min). The supernatant was collected for LC‐MS/MS analysis (Guo et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4‐FOXO1/SMS1 axis in sphingomyelin biosynthesis

et al. 2021

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Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well‐recognized. ROR2 plays an important role in aging‐related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self‐renewal capacity, while its overexpression in aged DPSCs restores their self‐renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4‐FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.

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Elucidating the mechanism of the surface functionalization dependent neurotoxicity of graphene family nanomaterials

Abstract: Graphene family nanomaterials (GFNs) have shown great potential for biological and environmental applications; however, their future use has been debated due to reported potential neurotoxicity. Moreover, the effects of surface...

Cited by 25 publications

References 25 publications

Stress Response and Nutrient Homeostasis in Lettuce (Lactuca sativa) Exposed to Graphene Quantum Dots Are Modulated by Particle Surface Functionalization

Stress Response and Nutrient Homeostasis in Lettuce (Lactuca sativa) Exposed to Graphene Quantum Dots Are Modulated by Particle Surface Functionalization

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model

Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4‐FOXO1/SMS1 axis in sphingomyelin biosynthesis

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