Cytotoxicity and physicochemical characterization of iron&amp;ndash;manganese-doped sulfated zirconia nanoparticles

Al-Fahdawi, Mohamed Qasim; Abdullah, Rasedee; Al‐Qubaisi, Mothanna Sadiq; Alhassan, Fatah H.; Rosli, Rozita; Zowalaty, Mohamed E. El; Naadja, Seif‑Eddine; Webster, Thomas J.; Taufiq‐Yap, Yun Hin

doi:10.2147/ijn.s82586

Cited by 12 publications

(5 citation statements)

References 44 publications

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“…Reduced graphene oxide modified by ZrO 2 NPs are used for highly sensitive electrochemical sensors for anticancer drugs ( Venu, et al, 2018 ). Iron-manganese-doped sulfated zirconia nanoparticles have been shown to induce HepG2 and MDA-MB-231 cell death, while they are less effective at killing normal Chang cells and HUVECs ( Al-Fahdawi, et al, 2015 ). Sulphated zirconia nanoparticles have significant cytotoxic effects on colon cancer HT29 cells ( Mftah, et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS

Shang

Wang

et al. 2021

Front. Chem.

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Zirconia nanoparticles (ZrO2 NPs) are commonly used in the field of biomedical materials, but their antitumor activity and mechanism is unclear. Herein, we evaluated the anti-tumor activity of ZrO2 NPs and explored the anti-tumor mechanism. The results of in vitro and in vivo experiments showed that the level of intracellular reactive oxygen species (ROS) in HeLa cells was elevated after ZrO2 NPs treatment. Transmission electron microscopy (TEM) showed that after treatment with ZrO2 NPs, the mitochondria of HeLa cells were swollen, accompanied with the induction of autophagic vacuoles. In addition, flow cytometry analysis showed that the apoptotic rate of HeLa cells increased significantly by Annexin staining after treatment with ZrO2 NPs, and the mitochondrial membrane potential (MMP) was reduced significantly. The proliferation of HeLa cells decreased as indicated by reduced Ki-67 labeling. In contrast, TUNEL-positive cells in tumor tissues increased after treatment with ZrO2 NPs, which is accompanied by increased expression of mitochondrial apoptotic proteins including Bax, Caspase-3, Caspase-9, and Cytochrome C (Cyt C) and increased expression of autophagy-related proteins including Atg5, Atg12, Beclin-1, and LC3-II. Treating HeLa cells with N-acetyl-L-cysteine (NAC) significantly reduced ROS, rate of apoptosis, MMP, and in vivo anti-tumor activity. In addition, apoptosis- and autophagy-related protein expressions were also suppressed. Based on these observations, we conclude that ZrO2 NPs induce HeLa cell death through ROS mediated mitochondrial apoptosis and autophagy.

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Section: Introductionmentioning

confidence: 99%

Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS

Shang

Wang

et al. 2021

Front. Chem.

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“…Conventionally, MTT assay has been applied to quantify cell viability in the presence of NPs at the concentrations between 0.001 and 100 μg/mL 26,44 , which are lower than those of our experimental conditions. The presence of other types of MO NPs such as ZnO, TiO 2 , and previously studied ZrO 2 at these lower concentrations caused significantly larger decreases in the MTT-based cell viability assay 45–48 . For example, ZnO and CuO NPs, which are often used in real-life applications, can decrease the viability of A549 cells to 30% of that of the control case.…”

Section: Resultsmentioning

confidence: 76%

Comparative study on the catalytic activity of Fe-doped ZrO2 nanoparticles without significant toxicity through chemical treatment under various pH conditions

Song

Hong

Lee

et al. 2019

Sci Rep

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Despite advances in the construction of catalysts based on metal oxide nanoparticles (MO NPs) for various industrial, biomedical, and daily-life applications, the biosafety concerns about these NPs still remain. Recently, the need to analyze and improve the safety of MO NPs along with attempts to enhance their catalytic performance has been strongly perceived. Here, we prepared multiple variants of Fe-doped zirconium oxide (Fe@ZrO 2 ) NPs under different pH conditions; then, we assessed their toxicity and finally screened the variant that exhibited the best catalytic performance. To assess the NP toxicity, the prepared NPs were introduced into three types of human cells originally obtained from different body parts likely to be most affected by NPs (skin, lung, and kidney). Experimental results from conventional cellular toxicity assays including recently available live-cell imaging indicated that none of the variants exerted severe negative effects on the viability of the human cells and most NPs were intracellular localized outside of nucleus, by which severe genotoxicity is unexpected. In contrast, Fe@ZrO 2 NPs synthesized under a basic condition (pH = 13.0), exhibited the highest catalytic activities for three different reactions; each was biochemical ( L -cysteine oxidation) or photochemical one (4-chlorophenol degradation and OH radical formation with benzoic acid). This study demonstrates that catalytic Fe@ZrO 2 NPs with enhanced activities and modest or insignificant toxicity can be effectively developed and further suggests a potential for the use of these particles in conventional chemical reactions as well as in recently emerging biomedical and daily-life nanotechnology applications.

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“…HepG2 cells (ATCCHB-8065) and Vero green monkey kidney cells (ATCCC1008) were used to test the cytotoxicity of the compound as previous described [ 23 ]. Cells were seeded in 96-well culture plates at a density of 5×10 3 cells per well.…”

Section: Methodsmentioning

confidence: 99%

IMB-XMA0038, a new inhibitor targeting aspartate-semialdehyde dehydrogenase of Mycobacterium tuberculosis

Wang

Yang

Liu

et al. 2021

Emerging Microbes & Infections

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The emergence of drug-resistant tuberculosis (TB) constitutes a major challenge to TB control programmes. There is an urgent need to develop effective anti-TB drugs with novel mechanisms of action. Aspartate-semialdehyde dehydrogenase (ASADH) is the second enzyme in the aspartate metabolic pathway. The absence of the pathway in humans and the absolute requirement of aspartate in bacteria make ASADH a highly attractive drug target. In this study, we used ASADH coupled with Escherichia coli type III aspartate kinase (LysC) to establish a high-throughput screening method to find new anti-TB inhibitors. IMB-XMA0038 was identified as an inhibitor of Mt ASADH with an IC 50 value of 0.59 μg/mL through screening. The interaction between IMB-XMA0038 and Mt ASADH was confirmed by surface plasmon resonance (SPR) assay and molecular docking analysis. Furthermore, IMB-XMA0038 was found to inhibit various drug-resistant MTB strains potently with minimal inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. The conditional mutant strain MTB:: asadh cultured with different concentrations of inducer (10 −5 or 10 −1 μg/mL pristinamycin) resulted in a maximal 16 times difference in MICs. At the same time, IMB-XMA0038 showed low cytotoxicity in vitro and vivo . In mouse model, it encouragingly declined the MTB colony forming units (CFU) in lung by 1.67 log10 dosed at 25 mg/kg for 15 days. In conclusion, our data demonstrate that IMB-XMA0038 is a promising lead compound against drug-resistant tuberculosis.

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Cytotoxicity and physicochemical characterization of iron–manganese-doped sulfated zirconia nanoparticles

Cited by 12 publications

References 44 publications

Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS

Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS

Comparative study on the catalytic activity of Fe-doped ZrO2 nanoparticles without significant toxicity through chemical treatment under various pH conditions

IMB-XMA0038, a new inhibitor targeting aspartate-semialdehyde dehydrogenase of Mycobacterium tuberculosis

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