Graphene oxide quantum dots disrupt autophagic flux by inhibiting lysosome activity in GC-2 and TM4 cell lines

Ji, Xiaoli; Xu, Bo; Yao, Mengmeng; Mao, Zhilei; Zhang, Yuqing; Xu, Guofeng; Tang, Qiusha; Wang, Xinru; Xia, Yankai

doi:10.1016/j.tox.2016.11.009

Cited by 57 publications

(33 citation statements)

References 40 publications

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“…It is essential to explore better materials for surface modification of scaffolds and guided bone regeneration in bone tissue engineering. As shown previously [26,27,33,34,36,39], both GO and GOQDs have good biocompatibility and the potential of differentiating stem cells towards osteoblastic lineage. However, whether GO or GOQDs could promote SHED osteogenic differentiation, and the different abilities of GO and GOQDs in inducing osteogenic differentiation of SHEDs remain unknown.…”

Section: Introductionsupporting

confidence: 56%

“…Unlike the ability of GO to absorb small molecules and some proteins from an osteogenic induction medium, which further proved its bioactivity, GOQDs can be ingested by cells and then influence cell behaviour [33]. Actually, most reports about GOQDs have been focused on their biomedical applications, for instance, biosensing [34], bioimaging [35], drug delivery [36] and photodynamic therapy [37]. Meanwhile, correlative research found graphene quantum dots' (GOQs) uptake by MSCs and effectively induced MSC osteogenic differentiation [38].…”

Section: Introductionmentioning

confidence: 99%

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Effects of graphene oxide and graphene oxide quantum dots on the osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Yang

Zhao

Chen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Graphene and its derivatives, graphene oxide (GO) and graphene oxide quantum dots (GOQDs), have recently attracted much attention as bioactive factors in differentiating stem cells towards osteoblastic lineage. The stem cells from human exfoliated deciduous teeth (SHEDs) possess the properties of selfrenewal, extensive proliferation, and multiple differentiation potential, and have gradually become one of the most promising mesenchymal stem cells (MSCs) in bone tissue engineering. The purpose of this study was to explore the effects of GO and GOQDs on the osteogenic differentiation of SHEDs. In this study, GO and GOQDs facilitated SHED proliferation up to 7 days in vitro at the concentration of 1 lg/ml. Because of their excellent fluorescent properties, GOQD uptake by SHEDs was confirmed and distributed in the SHED cytoplasm. Calcium nodules formation, alkaline phosphatase (ALP) activity, and RNA and protein expression increased significantly in SHEDs treated with osteogenic induction medium containing GOQDs but decreased with osteogenic induction medium containing GO. Interestingly, the Wnt/b-catenin signaling pathway appeared to be involved in osteogenic differentiation of SHEDs induced with GOQDs. In summary, GO and GOQDs at the concentration of 1 lg/ml promoted SHED proliferation. GOQDs induced the osteogenic differentiation of SHEDs, whilst GO slightly inhibited it.

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Section: Introductionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Effects of graphene oxide and graphene oxide quantum dots on the osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Yang

Zhao

Chen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…GOQDs possess intense emission and big absorptivity within NIR area, strong photobleaching resistance, and biocompatibility and big Stokes shift [21], as well as particular cell targeting competence [22], which renders them appropriate for imaging with detection's high sensitivity. Beyond fluorescent probe materials' superior properties [23], when they have been adopted within living organisms, it is also vital to know the interaction between cells and the materials [24].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Fluorescent labelling in living dental pulp stem cells by graphene oxide quantum dots

Guo

Ren

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Cellular labelling is possible to offer significant information after transplantation for the purpose of determining stem cell therapy's efficacy. According to the research, it has been reported that graphene oxide quantum dots (GOQDs) are a kind of healthy biological labelling agent for stem cells which show little cytotoxicity. GOQDs' interactions have been examined on the dental pulp stem cells (hDPSCs) of human beings for the purpose of investigating GOQD's biocompatibility and uptake and explored GOQDs' effects on hDPSCs' metabolic activity and the proliferation. According to the outcomes, GDQDs have been accepted by hDPSCs in a time-dependent and concentration-dependent behaviour. Moreover, no important changes have been discovered within hDOPSCs' proliferation, viability as well as metabolic activity after treatment with GOQDs. Therefore, such resources have shown that GOQDs can be multifunctional agents for cell therapy, drug delivery as well as cell imaging and also as outstanding candidates for labelling stem cells.

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“…Most evidence about autophagy dysfunction has focused on the termination stage of autophagic flux. For example, several nanoparticles, including AgNPs, raphene oxide quantum dots, and polymeric nanoparticles, suppresse the degradation of autophagosomes via lysosomal impairment [9,50,51]. In addition, Stern et al reported that nanoparticles could disrupt the cytoskeleton and prevent lysosomal trafficking, leading to autophagic flux blockage.…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticles induce autophagosome accumulation via activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes

Duan

et al. 2018

Autophagy

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Autophagy dysfunction is a potential toxic effect of nanoparticles. Previous studies have indicated that silica nanoparticles (SiNPs) induce macroautophagy/autophagy dysfunction, while the precise mechanisms remain uncertain. Hence, the present study investigated the molecular mechanisms by which SiNPs enhanced autophagosome synthesis, which then contributed to autophagy dysfunction. First, the effects of SiNPs on autophagy and autophagic flux were verified using transmission electron microscopy, laser scanning confocal microscopy, and western blot assays. Then, the activation of endoplasmic reticular (ER) stress was validated to be through the EIF2AK3 and ATF6 UPR pathways but not the ERN1-XBP1 pathway, along with the upregulation of downstream ATF4 and DDIT3. Thereafter, the ER stress inhibitor 4-phenylbutyrate (4-PBA) was used to verify that SiNP-induced autophagy could be influenced by ER stress. Furthermore, specialized lentiviral shRNA were employed to determine that autophagy was induced via specific activation of the EIF2AK3 and ATF6 UPR pathways. Finally, the 2 autophagic genes LC3B and ATG12 were found to be transcriptionally upregulated by downstream ATF4 and DDIT3 in ER stress, which contributed to the SiNP-enhanced autophagosome synthesis. Taken together, these data suggest that SiNPs induced autophagosome accumulation via the activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes, which offers a new insight into detailed molecular mechanisms underlying SiNP-induced autophagy dysfunction, and specifically how UPR pathways regulate key autophagic genes. This work provides novel evidence for the study of toxic effects and risk assessment of SiNPs.

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Graphene oxide quantum dots disrupt autophagic flux by inhibiting lysosome activity in GC-2 and TM4 cell lines

Cited by 57 publications

References 40 publications

Effects of graphene oxide and graphene oxide quantum dots on the osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Effects of graphene oxide and graphene oxide quantum dots on the osteogenic differentiation of stem cells from human exfoliated deciduous teeth

RETRACTED ARTICLE: Fluorescent labelling in living dental pulp stem cells by graphene oxide quantum dots

Silica nanoparticles induce autophagosome accumulation via activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes

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