Nitrogen-doped graphene quantum dots (N-GQDs) perturb redox-sensitive system via the selective inhibition of antioxidant enzyme activities in zebrafish

Deng, Shun; Fu, Ailing; Junaid, Muhammad; Wang, Yan; Yin, Qinyan; Fu, Chen; Liu, Li; Su, Dongsheng; Bian, Wan-Ping; Pei, De‐Sheng

doi:10.1016/j.biomaterials.2019.03.028

Cited by 61 publications

(25 citation statements)

References 75 publications

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“…Apart from iron overburden evidenced by a specific fluorescent probe, the disorder of redox homeostasis caused by N-GQDs were indicated by multiple indexes, including GSH depletion, decreased NADPH activity, excessive ROS production and LPO. Similar to other types of graphene-based nanoparticles or QDs, N-GQDs also has been found to be strongly capable of perturbing the redox-sensitive system by inhibiting specific antioxidant enzyme activities in model animals [ 9 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the toxicity studies on N-GQDs are underway and have not yet reached a consistent conclusion. Even though some researchers have suggested N-GQDs have low cytotoxicity [ 8 ], others show N-GQDs could be internalized into cells and disrupt some enzyme activities [ 9 ]. The N-GQDs, as fluorescent nanoprobes, could contribute to the development of nanotheranostics in the field of neuronscience due to their excellent optical properties, so it is significant to evaluate the interaction between N-GQDs and neurobiological models before applying them in living organisms.…”

Section: Introductionmentioning

confidence: 99%

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Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia

Liu

et al. 2020

Part Fibre Toxicol

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Background Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation. Results The cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis. Conclusion N-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia

Liu

et al. 2020

Part Fibre Toxicol

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“…The synthesized GQDs have a good range of size, strong luminescence emission and satisfactory properties. [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] 2.1 Top down methods 2.1.1 Liquid exfoliation. Liquid exfoliation (LE) of the 2D materials has drawn huge interest due to the scalability.…”

Section: Synthesis Of Gqdsmentioning

confidence: 99%

Graphene quantum dot based materials for sensing, bio-imaging and energy storage applications: a review

et al. 2020

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“…[36,38]. In some cases, the lack of any detected signal is the "required signal", as in those cases when the sensor must detect some agents that reduce enzyme activity [39][40][41][42]. Thus, it is mandatory to differentiate whether the enzyme has been inactivated by changes in the medium (e.g., drastic pH, or increase temperature) or it is really inhibited by the target compound.…”

Section: Introductionmentioning

confidence: 99%

Dextran Aldehyde in Biocatalysis: More Than a Mere Immobilization System

et al. 2019

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Dextran aldehyde (dexOx), resulting from the periodate oxidative cleavage of 1,2-diol moiety inside dextran, is a polymer that is very useful in many areas, including as a macromolecular carrier for drug delivery and other biomedical applications. In particular, it has been widely used for chemical engineering of enzymes, with the aim of designing better biocatalysts that possess improved catalytic properties, making them more stable and/or active for different catalytic reactions. This polymer possesses a very flexible hydrophilic structure, which becomes inert after chemical reduction; therefore, dexOx comes to be highly versatile in a biocatalyst design. This paper presents an overview of the multiple applications of dexOx in applied biocatalysis, e.g., to modulate the adsorption of biomolecules on carrier surfaces in affinity chromatography and biosensors design, to serve as a spacer arm between a ligand and the support in biomacromolecule immobilization procedures or to generate artificial microenvironments around the enzyme molecules or to stabilize multimeric enzymes by intersubunit crosslinking, among many other applications.

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Nitrogen-doped graphene quantum dots (N-GQDs) perturb redox-sensitive system via the selective inhibition of antioxidant enzyme activities in zebrafish

Cited by 61 publications

References 75 publications

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia

Graphene quantum dot based materials for sensing, bio-imaging and energy storage applications: a review

Dextran Aldehyde in Biocatalysis: More Than a Mere Immobilization System

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