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1
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Chen YC, Lin KYA, Chen YC, Hong YY, Hsu YF, Lin CH. Impact of photoaging on the chemical and cytotoxic properties of nanoscale zeolitic imidazolate framework-8. JOURNAL OF HAZARDOUS MATERIALS 2024; 479:135536. [PMID: 39191015 DOI: 10.1016/j.jhazmat.2024.135536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 08/29/2024]
Abstract
This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization.
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Affiliation(s)
- Yi-Chun Chen
- Department of Civil Engineering, National Taipei University of Technology, Taipei City 106, Taiwan; Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan
| | - Kun-Yi Andrew Lin
- Department of Environmental Engineering, National Chung Hsing University, Taichung 40227, Taiwan
| | - Yin-Chu Chen
- Department of Civil Engineering, National Taipei University of Technology, Taipei City 106, Taiwan
| | - Yan-Yu Hong
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan
| | - Yu-Fang Hsu
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan
| | - Chia-Hua Lin
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan.
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2
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Zhang Z, Wang Q, Zhang H, Wang S, Ma X, Wang H. Golm1 facilitates the CaO2-DOPC-DSPE200-PEI -CsPbBr3 QDs -induced apoptotic death of hepatocytes through the stimulation of mitochondrial autophagy and mitochondrial reactive oxygen species production through interactions with P53/Beclin-1/Bcl-2. Chem Biol Interact 2024; 398:111076. [PMID: 38815669 DOI: 10.1016/j.cbi.2024.111076] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 05/14/2024] [Accepted: 05/27/2024] [Indexed: 06/01/2024]
Abstract
Mitophagy is a distinct physiological process that can have beneficial or deleterious effects in particular tissues. Prior research suggests that mitophagic activity can be triggered by CaO2-PM-CsPbBr3 QDs, yet the specific role that mitophagy plays in hepatic injury induced by CaO2-PM-CsPbBr3 QDs has yet to be established. Accordingly, in this study a series of mouse model- and cell-based experiments were performed that revealed the ability of CaO2-PM-CsPbBr3 QDs to activate mitophagic activity. Golm1 was upregulated in response to CaO2-PM-CsPbBr3 QDs treatment, and overexpressing Golm1 induced autophagic flux in the murine liver and hepatocytes, whereas knocking down Golm1 had the opposite effect. CaO2-PM-CsPbBr3 QDs were also able to Golm1 expression, in turn promoting the degradation of P53 and decreasing the half-life of this protein. Overexpressing Golm1 was sufficient to suppress the apoptotic death of hepatocytes in vitro and in vivo, whereas the knockdown of Golm1 had the opposite effect. The ability of Golm1 to promote p53-mediated autophagy was found to be associated with the disruption of Beclin-1 binding to Bcl-2, and the Golm1 N-terminal domain was determined to be required for p53 interactions, inducing autophagic activity in a manner independent of helicase activity or RNA binding. Together, these results indicate that inhibiting Golm1 can promote p53-dependent autophagy via disrupting Beclin-1 binding to Bcl-2, highlighting a novel approach to mitigating liver injury induced by CaO2-PM-CsPbBr3 QDs.
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Affiliation(s)
- Zhiqiang Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450045, Henan Province, China.
| | - Qinglong Wang
- College of Animal Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan Province, China
| | - Haibo Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450045, Henan Province, China
| | - Shengchao Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450045, Henan Province, China
| | - Xia Ma
- College of Animal Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan Province, China
| | - Hui Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450045, Henan Province, China.
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3
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Das SK, Sen K, Ghosh B, Ghosh N, Sinha K, Sil PC. Molecular mechanism of nanomaterials induced liver injury: A review. World J Hepatol 2024; 16:566-600. [PMID: 38689743 PMCID: PMC11056894 DOI: 10.4254/wjh.v16.i4.566] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/05/2024] [Accepted: 03/19/2024] [Indexed: 04/24/2024] Open
Abstract
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
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Affiliation(s)
- Sanjib Kumar Das
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Koushik Sen
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Biswatosh Ghosh
- Department of Zoology, Bidhannagar College, Kolkata 700064, India
| | - Nabanita Ghosh
- Department of Zoology, Maulana Azad College, Kolkata 700013, India
| | - Krishnendu Sinha
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India.
| | - Parames C Sil
- Department of Molecular Medicine, Bose Institute, Calcutta 700054, India
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Yao Y, Zhang T, Tang M. The DNA damage potential of quantum dots: Toxicity, mechanism and challenge. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 317:120676. [PMID: 36395913 DOI: 10.1016/j.envpol.2022.120676] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 10/30/2022] [Accepted: 11/14/2022] [Indexed: 06/16/2023]
Abstract
Quantum dots (QDs) are semiconductor nanoparticles (1-10 nm) with excellent optical and electrical properties. As QDs show great promise for applications in fields such as biomedicine, their biosafety is widely emphasized. Therefore, studies on the potential 'nanotoxicity' of QDs in genetic material are warranted. This review summarizes and discusses recent reports derived from different cell lines or animal models concerning the effects of QDs on genetic material. QDs could induce many types of genetic material damage, which subsequently triggers a series of cellular adverse outcomes, including apoptosis, cell cycle arrest and senescence. However, the individual biological and ecological significance of the genotoxicity of QDs is not yet clear. In terms of mechanisms of genotoxicity, QDs can damage DNA either through their own nanomorphology or through the released metal ions. It also includes the reactive oxygen species generation, inflammation and failure of DNA damage repair. Notably, apoptosis may lead to false positive results in genotoxicity tests. Finally, given the different uses of QDs and the interference of the physicochemical properties of QDs on the test method, genotoxicity testing of QDs should be different from traditional toxic compounds, which requires further research.
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Affiliation(s)
- Yongshuai Yao
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, People's Republic of China
| | - Ting Zhang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, People's Republic of China
| | - Meng Tang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, People's Republic of China.
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5
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Lai CH, Chen YC, Lin KYA, Lin YX, Lee TH, Lin CH. Adverse pulmonary impacts of environmental concentrations of oil mist particulate matter in normal human bronchial epithelial cell. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 809:151119. [PMID: 34757100 DOI: 10.1016/j.scitotenv.2021.151119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/16/2021] [Accepted: 10/17/2021] [Indexed: 06/13/2023]
Abstract
Airborne oil mist particulate matter (OMPM) is generated during industrial processes such as metalworking and may be associated with pulmonary dysfunction. In this study, we employed the normal human bronchial epithelial BEAS-2B cell line to elucidate the association between pulmonary toxicity and OMPM of 2.5-10 μm, 1.0-2.5 μm and <1.0 μm particle sizes (OMPM10-2.5, OMPM2.5-1.0 and OMPM1.0). We measured OMPM concentrations at a precision machinery factory to estimate lung deposition rates and select realistic environmental concentrations for testing. All OMPMs (1-50 μg/cm2) significantly decreased BEAS-2B cell viability (>38% of control), except for low-dose OMPM1.0 (1 μg/cm2). OMPM10-2.5 and OMPM2.5-1.0, but not OMPM1.0, induced oxidative stress (1.5-4-fold increase compared with the control) and increased the production of proinflammatory cytokines (1.5-3-fold). However, only OMPM1.0 induced pulmonary epithelial barrier dysfunction via depletion of zonula occludens (0.65-0.8-fold) and α1-antitrypsin proteins (0.65-0.8-fold). In conclusion, a higher risk of lung disease was associated with smaller particle size OMPM. Exposure to OMPM1.0 may be a potential risk factor for chronic obstructive pulmonary disease. The evidence also demonstrates that occupational exposure to OMPM may cause pulmonary disease at very low concentrations.
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Affiliation(s)
- Chia-Hsiang Lai
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan
| | - Yi-Chun Chen
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan
| | - Kun-Yi Andrew Lin
- Department of Environmental Engineering, National Chung Hsing University, Taichung 40227, Taiwan
| | - Yi-Xian Lin
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan; Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
| | - Tsung-Han Lee
- Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
| | - Chia-Hua Lin
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan.
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6
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Cao W, Liu X, Huang X, Liu Z, Cao X, Gao W, Tang B. Hepatotoxicity-Related Oxidative Modifications of Thioredoxin 1/Peroxiredoxin 1 Induced by Different Cadmium-Based Quantum Dots. Anal Chem 2022; 94:3608-3616. [PMID: 35179864 DOI: 10.1021/acs.analchem.1c05181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The hepatotoxicity of cadmium-based quantum dots (Cd-QDs) has become the focus with their extensive applications in biomedicine. Previous reports have demonstrated that high oxidative stress and consequent redox imbalance play critical roles in their toxicity mechanisms. Intracellular antioxidant proteins, such as thioredoxin 1 (Trx1) and peroxiredoxin 1 (Prx1), could regulate redox homeostasis through thiol-disulfide exchange. Herein, we hypothesized that the excessive reactive oxygen species (ROS) induced by Cd-QD exposure affects the functions of Trx1 or Prx1, which further causes abnormal apoptosis of liver cells and hepatotoxicity. Thereby, three types of Cd-QDs, CdS, CdSe, and CdTe QDs, were selected for conducting an intensive study. Under the same conditions, the H2O2 level in the CdTe QD group was much higher than that of CdS or CdSe QDs, and it also corresponded to the higher hepatotoxicity. Mass spectrometry (MS) results show that excessive H2O2 leads to sulfonation modification (-SO3H) at the active sites of Trx1 (Cys32 and Cys35) and Prx1 (Cys52 and Cys173). The irreversible oxidative modifications broke their cross-linking with the apoptosis signal-regulating kinase 1 (ASK1), resulting in the release and activation of ASK1, and activation of the downstream JNK/p38 signaling finally promoted liver cell apoptosis. These results highlight the key effect of the high oxidative stress, which caused irreversible oxidative modifications of Trx1 and Prx1 in the mechanisms involved in Cd-QD-induced hepatotoxicity. This work provides a new perspective on the hepatotoxicity mechanisms of Cd-QDs and helps design safe and reliable Cd-containing nanoplatforms.
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Affiliation(s)
- Wenhua Cao
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Xiaoqian Liu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Xiaoqing Huang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Zhenhua Liu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Xinyi Cao
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Wen Gao
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China
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7
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Pang Y, Wu D, Ma Y, Cao Y, Liu Q, Tang M, Pu Y, Zhang T. Reactive oxygen species trigger NF-κB-mediated NLRP3 inflammasome activation involvement in low-dose CdTe QDs exposure-induced hepatotoxicity. Redox Biol 2021; 47:102157. [PMID: 34614473 PMCID: PMC8489155 DOI: 10.1016/j.redox.2021.102157] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/17/2021] [Accepted: 09/28/2021] [Indexed: 02/07/2023] Open
Abstract
Cadmium telluride (CdTe) quantum dots (QDs) can be employed as imaging and drug delivery tools; however, the toxic effects and mechanisms of low-dose exposure are unclear. Therefore, this pioneering study focused on hepatic macrophages (Kupffer cells, KCs) and explored the potential damage process induced by exposure to low-dose CdTe QDs. In vivo results showed that both 2.5 μM/kg·bw and 10 μM/kg·bw could both activate KCs to cause liver injury, and produce inflammation by disturbing antioxidant levels. Abnormal liver function further verified the risks of low-dose exposure to CdTe QDs. The KC model demonstrated that low-dose CdTe QDs (0 nM, 5 nM and 50 nM) can be absorbed by cells and cause severe reactive oxygen species (ROS) production, oxidative stress, and inflammation. Additionally, the expression of NF-κB, caspase-1, and NLRP3 were decreased after pretreatment with ROS scavenging agent N-acetylcysteine (NAC, 5 mM pretreated for 2 h) and the NF-κB nuclear translocation inhibitor Dehydroxymethylepoxyquinomicin (DHMEQ, 10 μg/mL pretreatment for 4 h) respectively. The results indicate that the activation of the NF-κB pathway by ROS not only directly promotes the expression of inflammatory factors such as pro-IL-1β, TNF-α, and IL-6, but also mediates the assembly of NLRP3 by ROS activation of NF-κB pathway, which indirectly promotes the expression of NLRP3. Finally, a high-degree of overlap between the expression of the NF-κB and NLRP3 and the activated regions of KCs, further support the importance of KCs in inflammation induced by low-dose CdTe QDs.
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Affiliation(s)
- Yanting Pang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Daming Wu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Ying Ma
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yuna Cao
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Qing Liu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Meng Tang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yuepu Pu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Ting Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
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8
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Liang Y, Zhang T, Tang M. Toxicity of quantum dots on target organs and immune system. J Appl Toxicol 2021; 42:17-40. [PMID: 33973249 DOI: 10.1002/jat.4180] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/22/2021] [Accepted: 04/22/2021] [Indexed: 11/06/2022]
Abstract
Quantum dots (QDs), due to their superior luminous properties, have been proven to be a very promising biological probe, which can be used as a candidate material for clinical applications. The toxicity of QDs in the environment and biological systems has caused widespread concern in the nanosphere, but their immune toxicity and their impact on the immune system are still relatively unknown. At present, the research on the toxicity of QDs is mainly focused on in vitro models, but few have systematically evaluated their adverse effects on target organs. Animal studies have shown that QDs can be accumulated in various organs due to their main exposure routes, thereby posing a potential threat to major organs. This review briefly describes general characteristics and the wide medical applications of QDs and focuses on the adverse effects of QDs on major target organs, such as liver, lung, kidney, brain, and spleen, after acute and chronic exposure. QDs mainly cause changes in the corresponding indicators of target organs, such as oxidative damage, and in severe cases cause hyperemia, tissue necrosis, and even death. In addition to causing direct damage to target organs, QDs can also cause a large number of immune cells to accumulate and cause inflammatory reactions when causing damage to other major organs. Whether it is to avoid the risk of people contacting QDs in production and life, or to realize the clinical applications of QDs, is very essential to conduct systematic in vivo toxicity assessment of QDs.
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Affiliation(s)
- Ying Liang
- Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Tao Zhang
- Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, China
| | - Meng Tang
- Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
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9
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One-pot bioinspired synthesis of fluorescent metal chalcogenide and carbon quantum dots: Applications and potential biotoxicity. Colloids Surf B Biointerfaces 2021; 200:111578. [DOI: 10.1016/j.colsurfb.2021.111578] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/09/2021] [Accepted: 01/11/2021] [Indexed: 12/18/2022]
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10
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Wang L, Zhao J, Cui L, Li YF, Li B, Chen C. Comparative nanometallomics as a new tool for nanosafety evaluation. Metallomics 2021; 13:6189688. [PMID: 33770173 DOI: 10.1093/mtomcs/mfab013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/27/2021] [Accepted: 03/19/2021] [Indexed: 11/14/2022]
Abstract
Nanosafety evaluation is paramount since it is necessary not only for human health protection and environmental integrity but also as a cornerstone for industrial and regulatory bodies. The current nanometallomics did not cover non-metallic nanomaterials, which is an important part of nanomaterials. In this critical review, the concept of nanometallomics was expanded to incorporate all nanomaterials. The impacts on metal(loid) and metallo-biomolecular homeostasis by nanomaterials will be focused upon in nanometallomics study. Besides, the impacts on elemental and biomolecular homeostasis by metallo-nanomaterials are also considered as the research subjects of nanometallomics. Based on the new concept of nanometallomics, comparative nanometallomics was proposed as a new tool for nanosafety evaluation, which is high throughput and will be precise considering the nature of machine learning techniques. The perspectives of nanometallomics like metallo-wide association study and non-target nanometallomics were put forward.
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Affiliation(s)
- Liming Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; CAS-HKU Joint Laboratory of Metallomics on Health and Environment; Beijing Metallomics Facility; National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jiating Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; CAS-HKU Joint Laboratory of Metallomics on Health and Environment; Beijing Metallomics Facility; National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Liwei Cui
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yu-Feng Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; CAS-HKU Joint Laboratory of Metallomics on Health and Environment; Beijing Metallomics Facility; National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Bai Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; CAS-HKU Joint Laboratory of Metallomics on Health and Environment; Beijing Metallomics Facility; National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
| | - Chunying Chen
- University of Chinese Academy of Sciences, Beijing 100049, China.,CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
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11
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Hu L, Zhong H, He Z. Toxicity evaluation of cadmium-containing quantum dots: A review of optimizing physicochemical properties to diminish toxicity. Colloids Surf B Biointerfaces 2021; 200:111609. [PMID: 33588242 DOI: 10.1016/j.colsurfb.2021.111609] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/25/2021] [Accepted: 02/02/2021] [Indexed: 02/06/2023]
Abstract
Fluorescent quantum dots (QDs) have received extensive attention because of their excellent optical properties and wide utilization in biological and biomedical areas. Nonetheless, there have been intense concerns on the cytotoxicity assessment of cadmium-containing QDs due to free cadmium ions release and nano-size effects. This paper reviews the representative synthetic strategies for preparation of cadmium-containing QDs and their applications. Then the toxicity assessments of QDs from cell studies to animal models are discussed, which can aid in improving our understanding of the cytotoxicity of QDs, and the toxicity mechanism is proposed. Several critical physicochemical properties of QDs are discussed and suggestions are provided for optimizing QDs design in view of minimal cytotoxicity. Finally, accurate detection techniques and systematic methodologies for the toxicity assessment of QDs are expected to achieve further breakthroughs in the future, especially in-situ, real-time, and rapid quantitative analysis methods.
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Affiliation(s)
- Liang Hu
- School of Minerals Processing and Bioengineering, Key Laboratory of Biohydrometallurgy of Ministry of Education, Central South University, Changsha, 410083, China
| | - Hui Zhong
- School of Life Science, Central South University, Changsha, 410012, China.
| | - Zhiguo He
- School of Minerals Processing and Bioengineering, Key Laboratory of Biohydrometallurgy of Ministry of Education, Central South University, Changsha, 410083, China.
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12
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Liu N, Tang M. Toxicity of different types of quantum dots to mammalian cells in vitro: An update review. JOURNAL OF HAZARDOUS MATERIALS 2020; 399:122606. [PMID: 32516645 DOI: 10.1016/j.jhazmat.2020.122606] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 03/23/2020] [Accepted: 03/27/2020] [Indexed: 05/18/2023]
Abstract
Currently, there are a great quantity type of quantum dots (QDs) that has been developed by researchers. Depending on the core material, they can be roughly divided into cadmium, silver, indium, carbon and silicon QDs. And studies on the toxicity of QDs are also increasing rapidly, but in vivo tests in model animals fail to reach a consistent conclusion. Therefore, we review the literatures dealing with the cytotoxicity of QDs in mammalian cells in vitro. After a short summary of the application characteristics of five types of QDs, the fate of QDs in cells will be discussed, ranging from the uptake, transportation, sublocation and excretion. A substantial part of the review will be focused on in vitro toxicity, in which the type of QDs is combined with their adverse effect and toxic mechanism. Because of their different luminescent properties, different subcellular fate, and different degree of cytotoxicity, we provide an overview on the balance of optical stability and biocompatibility of QDs and give a short outlook on future direction of cytotoxicology of QDs.
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Affiliation(s)
- Na Liu
- Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, PR China.
| | - Meng Tang
- Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, PR China.
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Yaghini E, Tacconi E, Pilling A, Rahman P, Broughton J, Naasani I, Keshtgar MRS, MacRobert AJ, Della Pasqua O. Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies. Eur J Pharm Sci 2020; 157:105639. [PMID: 33188925 PMCID: PMC8214104 DOI: 10.1016/j.ejps.2020.105639] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 10/26/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022]
Abstract
There is considerable interest in biomedical applications of quantum dot (QD) nanoparticles, in particular their use as imaging agents for diagnostic applications. In order to investigate the in vivo biodistribution and the potential toxicity of quantum dots (QDs), it is crucial to develop pharmacokinetic (PK) models as basis for prediction of QDs exposure profiles over time. Here, we investigated the in vivo biodistribution of novel indium-based QDs in mice for up to three months after intravenous administration and subsequently developed a translational population PK model to scale findings to humans. This evaluation was complemented by a comprehensive overview of the in vivo toxicology of QDs in rats. The QDs were primarily taken up by the liver and spleen and were excreted via hepatobiliary and urinary pathways. A non-linear mixed effects modelling approach was used to describe blood and organ disposition characteristics of QDs using a multi-compartment PK model. The observed blood and tissue exposure to QDs was characterised with an acceptable level of accuracy at short and long-term. Of note is the fast distribution of QDs from blood into liver and spleen in the first 24 h post-injection (half-life of 28 min) followed by a long elimination profile (half-life range: 47-90 days). This is the first study to assess the PK properties of QDs using a population pharmacokinetic approach to analyse in vivo preclinical data. No organ damage was observed following systemic administration of QDs at doses as high as 48 mg/kg at 24 h, 1 week and 5 weeks post-injection. In conjunction with the data arising from the toxicology experiments, PK parameter estimates provide insight into the potential PK properties of QDs in humans, which ultimately allow prediction of their disposition and enable optimisation of the design of first-in-human QDs studies.
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Affiliation(s)
- Elnaz Yaghini
- UCL Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.
| | - Elisa Tacconi
- Clinical Pharmacology and Therapeutics Group, University College London, School of Pharmacy, BMA House, Tavistock Square, London, WC1H 9JP, UK
| | - Andrew Pilling
- ToxPath Consultancy Ltd, Church Road, Wingfield, Diss, IP21 5RA, UK
| | - Paula Rahman
- Nanoco Technologies Ltd, 46 Grafton Street, Manchester M13 9NT, UK
| | - Joe Broughton
- Nanoco Technologies Ltd, 46 Grafton Street, Manchester M13 9NT, UK
| | - Imad Naasani
- Nanoco Technologies Ltd, 46 Grafton Street, Manchester M13 9NT, UK
| | - Mohammed R S Keshtgar
- UCL Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK
| | - Alexander J MacRobert
- UCL Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK
| | - Oscar Della Pasqua
- Clinical Pharmacology and Therapeutics Group, University College London, School of Pharmacy, BMA House, Tavistock Square, London, WC1H 9JP, UK
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14
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Vilas-Boas V, Vinken M. Hepatotoxicity induced by nanomaterials: mechanisms and in vitro models. Arch Toxicol 2020; 95:27-52. [PMID: 33155068 DOI: 10.1007/s00204-020-02940-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/20/2020] [Indexed: 12/14/2022]
Abstract
The unique physicochemical properties of materials at nanoscale have opened a plethora of opportunities for applications in the pharmaceutical and medical field, but also in consumer products from food and cosmetics industries. As a consequence, daily human exposure to nanomaterials through distinct routes is considerable and, therefore, may raise health concerns. Many nanomaterials have been described to accumulate and induce adversity in the liver. Among these, silica and some types of metallic nanoparticles are the most broadly used in consumer products and, therefore, the most studied and reported. The reviewed literature was collected from PubMed.gov during the month of March 2020 using the search words "nanomaterials induced hepatotoxicity", which yielded 181 papers. This present paper reviews the hepatotoxic effects of nanomaterials described in in vitro and in vivo studies, with emphasis on the underlying mechanisms. The induction of oxidative stress and inflammation are the manifestations of toxicity most frequently reported following exposure of cells or animal models to different nanomaterials. Furthermore, the available in vitro models for the evaluation of the hepatotoxic effects of nanomaterials are discussed, highlighting the continuous interest in the development of more advanced and reliable in vitro models for nanotoxicology.
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Affiliation(s)
- Vânia Vilas-Boas
- Department of In Vitro Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
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15
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Luo YH, Cheng HJ, Tsai FY, Tsou TC, Lin SY, Lin P. Primary Amine Modified Gold Nanodots Regulate Macrophage Function and Antioxidant Response: Potential Therapeutics Targeting of Nrf2. Int J Nanomedicine 2020; 15:8411-8426. [PMID: 33149584 PMCID: PMC7605661 DOI: 10.2147/ijn.s268203] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 10/02/2020] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Gold nanoparticles with high biocompatibility and immunomodulatory properties have potential applications in the development of new diagnostic and therapeutic strategies for nanomedicine. Nanoparticles targeting macrophages can manipulate or control immunological diseases. This study assessed the activity of dendrimer-encapsulated gold nanodots (AuNDs) with three surface modifications [ie, outfacing groups with primary amine (AuNDs-NH2), hydroxyl (AuNDs-OH), and quaternary ammonium ions (AuNDs-CH3)] regulated macrophage function and antioxidant response through Nrf2-dependent pathway. METHODS AuNDs were prepared and characterized. Intracellular distribution of AuNDs in human macrophages was observed through confocal microscopy. The activity of AuNDs was evaluated using macrophage functions and antioxidant response in the human macrophage cell line THP-1. RESULTS AuNDs-NH2 and AuNDs-CH3, but not AuNDs-OH, drove the obvious Nrf2-antioxidant response element pathway in THP-1 cells. Of the three, AuNDs-NH2 considerably increased mRNA levels and antioxidant activities of heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in THP-1 cells. IL-6 mRNA and protein expression was mediated through Nrf2 activation in AuNDs-NH2-treated macrophages. Furthermore, Nrf2 activation by AuNDs-NH2 increased the phagocytic ability of THP-1 macrophages. CONCLUSION AuNDs-NH2 had immunomodulatory activities in macrophages. The findings of the present work suggested that AuNDs have potential effects against chronic inflammatory diseases via the Nrf2 pathway.
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Affiliation(s)
- Yueh-Hsia Luo
- Department of Life Sciences, National Central University, Taoyuan City32001, Taiwan
| | - Hsien-Jen Cheng
- National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County35053, Taiwan
| | - Feng-Yuan Tsai
- National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County35053, Taiwan
| | - Tsui-Chun Tsou
- National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County35053, Taiwan
| | - Shu-Yi Lin
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County35053, Taiwan
| | - Pinpin Lin
- National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County35053, Taiwan
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16
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Nguyen KC, Zhang Y, Todd J, Kittle K, Lalande M, Smith S, Parks D, Navarro M, Tayabali AF, Willmore WG. Hepatotoxicity of Cadmium Telluride Quantum Dots Induced by Mitochondrial Dysfunction. Chem Res Toxicol 2020; 33:2286-2297. [PMID: 32844644 DOI: 10.1021/acs.chemrestox.9b00526] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The aim of this study was to investigate the detailed mechanisms of hepatotoxicity induced by cadmium telluride quantum dots (CdTe-QDs) in BALB/c mice after intravenous injection. The study investigated oxidative stress, apoptosis, and effects on mitochondria as potential mechanistic events to elucidate the observed hepatotoxicity. Oxidative stress in the liver, induced by CdTe-QD exposure, was demonstrated by depletion of total glutathione, an increase in superoxide dismutase activity, and changes in the gene expression of several oxidative stress-related biomarkers. Furthermore, CdTe-QD treatment led to apoptosis in the liver via both intrinsic and extrinsic apoptotic pathways. Effects on mitochondria were evidenced by the enlargement and increase in the number of mitochondria in hepatocytes of treated mice. CdTe-QDs also caused changes in the levels and gene expression of electron transport chain enzymes, depletion of ATP, and an increase in the level of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis. The findings from this study suggest that CdTe-QDs-induced hepatotoxicity might have originated from mitochondrial effects which resulted in oxidative stress and apoptosis in the liver cells. This study provides insight into the biological effects of CdT-QDs at the tissue level and the detailed mechanisms of their toxicity in animals. The study also provides important data for bridging the gap between in vitro and in vivo testing and risk assessment of these NPs.
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Affiliation(s)
- Kathy C Nguyen
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario K1A 0K9, Canada.,Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada
| | - Yan Zhang
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario K1A 0K9, Canada
| | - Julie Todd
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Kevin Kittle
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Michelle Lalande
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Scott Smith
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Douglas Parks
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Martha Navarro
- Bureau of Chemical Safety, Health Products and Food Branch, Frederick G. Banting Building, Health Canada, Ottawa, Ontario K1A 0K9, Canada
| | - Azam F Tayabali
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario K1A 0K9, Canada.,Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada
| | - William G Willmore
- Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada
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17
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Chen B, Hong W, Yang P, Tang Y, Zhao Y, Aguilar ZP, Xu H. Nano Zinc Oxide Induced Fetal Mice Growth Restriction, Based on Oxide Stress and Endoplasmic Reticulum Stress. NANOMATERIALS 2020; 10:nano10020259. [PMID: 32024284 PMCID: PMC7075166 DOI: 10.3390/nano10020259] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/23/2020] [Accepted: 01/31/2020] [Indexed: 12/20/2022]
Abstract
ZnO NPs have been assessed to show adverse effects on reproductive organs, but the molecular mechanisms of reproductive toxicity have not been sufficiently studied. In this research, the dosage effects from the oral exposure of ZnO NPs (30 nm) to pregnant mice in gestation day 10.5 to 17.5 was analyzed. Pregnant mice exposed to ZnO NPs induced dam injury, mice fetal growth restriction, and the fetus number decreased. The pathological evaluation showed that ZnO NPs exposure caused placental spongiotrophoblast area decease and structural damage. The RT-qPCR and immunocytochemistry data indicated that ZnO NPs could induce placenta oxide stress, endoplasmic reticulum stress responses, apoptosis, and altered placental function. These findings indicated that ZnO NPs could induce dam injury and fetal growth restriction. Reproductive toxicity of ZnO NPs may be due to placental injury and function alteration caused by apoptosis, oxide stress, and endoplasmic reticulum stress after ZnO NPs exposure.
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Affiliation(s)
- Bolu Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
| | - Wuding Hong
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
| | - Pengfei Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
| | - Yizhou Tang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
| | - Yu Zhao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
| | | | - Hengyi Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (B.C.); (W.H.); (P.Y.); (Y.T.); (Y.Z.)
- Correspondence: ; Tel.: +0086-791-8830-4447 ext. 9520; Fax: +008s6-791-8830-4400
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18
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Nguyen KC, Zhang Y, Todd J, Kittle K, Patry D, Caldwell D, Lalande M, Smith S, Parks D, Navarro M, Massarsky A, Moon TW, Willmore WG, Tayabali AF. Biodistribution and Systemic Effects in Mice Following Intravenous Administration of Cadmium Telluride Quantum Dot Nanoparticles. Chem Res Toxicol 2019; 32:1491-1503. [DOI: 10.1021/acs.chemrestox.8b00397] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Kathy C. Nguyen
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario, Canada K1A 0K9
- Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario Canada, K1S 5B6
| | - Yan Zhang
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario, Canada K1A 0K9
| | - Julie Todd
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Kevin Kittle
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Dominique Patry
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Don Caldwell
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Michelle Lalande
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Scott Smith
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Douglas Parks
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Martha Navarro
- Bureau of Chemical Safety, Health Products and Food Branch, 251 Sir Frederick Banting Driveway, Health Canada, Ottawa, Ontario, Canada K1A 0K9
| | - Andrey Massarsky
- University of Ottawa, Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, 75 Laurier Avenue East, Ottawa, Ontario, Canada K1N 6N5
| | - Thomas W. Moon
- University of Ottawa, Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, 75 Laurier Avenue East, Ottawa, Ontario, Canada K1N 6N5
| | - William G. Willmore
- Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario Canada, K1S 5B6
| | - Azam F. Tayabali
- Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, Ontario, Canada K1A 0K9
- Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario Canada, K1S 5B6
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19
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Lu J, Tang M, Zhang T. Review of toxicological effect of quantum dots on the liver. J Appl Toxicol 2018; 39:72-86. [PMID: 30091143 DOI: 10.1002/jat.3660] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 05/10/2018] [Accepted: 06/04/2018] [Indexed: 12/31/2022]
Abstract
In recent years, quantum dots (QDs) have potential applications in technology, research and medicine. The small particle size is coupled to their unique chemical and physical properties and their excellent fluorescence characteristics. A growing number of studies have shown that QDs are distributed to secondary organs through multiple pathways, while the liver is the main reservoir of QDs. Here, we review current liver toxicity studies of QDs in vivo and in vitro. Mechanisms of hepatotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into animal studies is highlighted. In this context, there still exists significant discrepancies between in vitro and in vivo results, and the specific toxicity mechanism remains unclear. The hepatotoxicities of QDs are the need for a unifying protocol for reliable and realistic toxicity reports.
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Affiliation(s)
- Jie Lu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University and Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210009, China
| | - Meng Tang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University and Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210009, China
| | - Ting Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University and Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210009, China
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20
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Yaghini E, Turner H, Pilling A, Naasani I, MacRobert AJ. In vivo biodistribution and toxicology studies of cadmium-free indium-based quantum dot nanoparticles in a rat model. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2018; 14:2644-2655. [PMID: 30048815 PMCID: PMC6198065 DOI: 10.1016/j.nano.2018.07.009] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/02/2018] [Accepted: 07/17/2018] [Indexed: 12/31/2022]
Abstract
Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However, toxicity concerns about commonly used cadmium-based QDs hinder their translation to clinical applications. In this study we describe the in vivo biodistribution and toxicology of indium-based water soluble QDs in rats following intravenous administration. The biodistribution measured at up to 90 days showed that QDs mainly accumulated in the liver and spleen, with similar elimination kinetics to subcutaneous administration. Evidence for QD degradation in the liver was found by comparing photoluminescence measurements versus elemental analysis. No organ damage or histopathological lesions were observed for the QDs treated rats after 24 h, 1 and 4 weeks following intravenous administration at 12.5 mg/kg or 50 mg/kg. Analysis of serum biochemistry and complete blood counts found no toxicity. This work supports the strong potential of indium-based QDs for translation into the clinic.
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Affiliation(s)
- Elnaz Yaghini
- Division of Surgery and Interventional Science, University College London, London, UK.
| | | | - Andrew Pilling
- ToxPath Consultancy Limited, Stradbroke Business Centre, Eye, Suffolk, UK
| | | | - Alexander J MacRobert
- Division of Surgery and Interventional Science, University College London, London, UK
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21
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Fan J, Wang S, Zhang X, Chen W, Li Y, Yang P, Cao Z, Wang Y, Lu W, Ju D. Quantum Dots Elicit Hepatotoxicity through Lysosome-Dependent Autophagy Activation and Reactive Oxygen Species Production. ACS Biomater Sci Eng 2018; 4:1418-1427. [PMID: 33418671 DOI: 10.1021/acsbiomaterials.7b00824] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Jiajun Fan
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Shaofei Wang
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Xuyao Zhang
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Wei Chen
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Yubin Li
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Ping Yang
- Instrumental Analysis Center, School of Pharmacy, Fudan University, Shanghai, 201203, P. R. China
| | - Zhonglian Cao
- Instrumental Analysis Center, School of Pharmacy, Fudan University, Shanghai, 201203, P. R. China
| | - Yichen Wang
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Weiyue Lu
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
| | - Dianwen Ju
- Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, P. R. China
- Department of Microbiological and Biochemical Pharmacy and Key Lab of Smart Drug Delivery MOE, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China
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22
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Yang L, Wang WC, Lung SCC, Sun Z, Chen C, Chen JK, Zou Q, Lin YH, Lin CH. Polycyclic aromatic hydrocarbons are associated with increased risk of chronic obstructive pulmonary disease during haze events in China. THE SCIENCE OF THE TOTAL ENVIRONMENT 2017; 574:1649-1658. [PMID: 27614859 DOI: 10.1016/j.scitotenv.2016.08.211] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 07/28/2016] [Accepted: 08/31/2016] [Indexed: 06/06/2023]
Abstract
Although exposure to particulate matter with a diameter of <2.5μm (PM2.5) is associated with chronic obstructive pulmonary disease (COPD), the major components of PM2.5 in COPD pathogenesis are controversial. Here we employed the human lung epithelial cell line BEAS-2B to elucidate the association between COPD and the organic and water-soluble components of PM2.5. We found that the PM2.5 organic extract was a potential major risk factor for pulmonary epithelial barrier dysfunction through the depletion of proteins from the zonula occludens. This extract induced severe oxidative stress that increased DNA damage and the production of proinflammatory cytokines by BEAS-2B cells as well as decreased α1-antitrypsin expression, suggesting a mechanism that increases the risk of COPD. These effects were mainly mediated by polycyclic aromatic hydrocarbons (PAHs) through the aryl hydrocarbon receptor pathway. PAHs with high benzo(a)pyrene (BaP)-equivalent concentrations, but not major PAH components, have an increased risk of causing COPD, suggesting that BaP-equivalent concentrations represent a PM2.5-induced COPD risk metric, which may contribute to provide a rationale for the remediation of air pollution.
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Affiliation(s)
- Lingyan Yang
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Wen-Cheng Wang
- Research Center for Environmental Changes, Academia Sinica, Taipei 11529, Taiwan
| | | | - Zhelin Sun
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Chongjun Chen
- School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Jen-Kun Chen
- Institute of Biomedical Engineering & Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan
| | - Qiang Zou
- Suzhou Environmental Monitor Center, Suzhou 215004, China
| | - Yu-Hsin Lin
- Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei 11174, Taiwan
| | - Chia-Hua Lin
- Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan.
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23
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Reiss P, Carrière M, Lincheneau C, Vaure L, Tamang S. Synthesis of Semiconductor Nanocrystals, Focusing on Nontoxic and Earth-Abundant Materials. Chem Rev 2016; 116:10731-819. [DOI: 10.1021/acs.chemrev.6b00116] [Citation(s) in RCA: 274] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Peter Reiss
- Université Grenoble Alpes, INAC-SyMMES, F-38054 Grenoble Cedex 9, France
- CEA, INAC-SyMMES-STEP/LEMOH, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France
- CNRS, SPrAM, F-38054 Grenoble Cedex 9, France
| | - Marie Carrière
- Université Grenoble Alpes, INAC-SyMMES, F-38054 Grenoble Cedex 9, France
- CEA, INAC-SyMMES-CIBEST/LAN, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France
| | - Christophe Lincheneau
- Université Grenoble Alpes, INAC-SyMMES, F-38054 Grenoble Cedex 9, France
- CEA, INAC-SyMMES-STEP/LEMOH, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France
- CNRS, SPrAM, F-38054 Grenoble Cedex 9, France
| | - Louis Vaure
- Université Grenoble Alpes, INAC-SyMMES, F-38054 Grenoble Cedex 9, France
- CEA, INAC-SyMMES-STEP/LEMOH, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France
- CNRS, SPrAM, F-38054 Grenoble Cedex 9, France
| | - Sudarsan Tamang
- Department
of Chemistry, Sikkim University, Sikkim 737102, India
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24
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CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation. Biomaterials 2016; 90:27-39. [DOI: 10.1016/j.biomaterials.2016.03.003] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 02/23/2016] [Accepted: 03/01/2016] [Indexed: 01/08/2023]
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25
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Iavicoli I, Fontana L, Nordberg G. The effects of nanoparticles on the renal system. Crit Rev Toxicol 2016; 46:490-560. [DOI: 10.1080/10408444.2016.1181047] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Ivo Iavicoli
- Section of Occupational Medicine, Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Luca Fontana
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene INAIL-Italian Workers’ Compensation Authority, Monte Porzio Catone (Rome), Italy
| | - Gunnar Nordberg
- Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden
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26
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Ho CC, Luo YH, Chuang TH, Lin P. Quantum dots induced interferon beta expression via TRIF-dependent signaling pathways by promoting endocytosis of TLR4. Toxicology 2016; 344-346:61-70. [PMID: 26925925 DOI: 10.1016/j.tox.2016.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 02/22/2016] [Accepted: 02/25/2016] [Indexed: 02/06/2023]
Abstract
Quantum dots (QDs) are nano-sized semiconductors. Previously, intratracheal instillation of QD705s induces persistent inflammation and remodeling in the mouse lung. Expression of interferon beta (IFN-β), involved in tissue remodeling, was induced in the mouse lung. The objective of this study was to understand the mechanism of QD705 induced interferon beta (IFN-β) expression. QD705-COOH and QD705-PEG increased IFN-β and IP-10 mRNA levels during day 1 to 90 post-exposure in mouse lungs. QD705-COOH increased IFN-β expression via Toll/interleukin-1 receptor domain-containing adapter protein (TRIF) dependent Toll-like receptor (TLR) signaling pathways in macrophages RAW264.7. Silencing TRIF expression with siRNA or co-treatment with a TRIF inhibitor tremendously abolished QD705s-induced IFN-β expression. Co-treatment with a TLR4 inhibitor completely prevented IFN-β induction by QD705-COOH. QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented IFN-β induction. Thus, activation of the TRIF dependent TLRs pathway by promoting endocytosis of TLR4 is one of the mechanisms for immunomodulatory effects of nanoparticles.
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Affiliation(s)
- Chia-Chi Ho
- National Institutes of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC
| | - Yueh-Hsia Luo
- National Institutes of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC
| | - Tsung-Hsien Chuang
- Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan, ROC
| | - Pinpin Lin
- National Institutes of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan, ROC.
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27
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Yang Y, Lv SY, Yu B, Xu S, Shen J, Zhao T, Zhang H. Hepatotoxicity assessment of Mn-doped ZnS quantum dots after repeated administration in mice. Int J Nanomedicine 2015; 10:5787-96. [PMID: 26396512 PMCID: PMC4576905 DOI: 10.2147/ijn.s88789] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future.
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Affiliation(s)
- Yanjie Yang
- Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, People's Republic of China ; School of Medicine, Henan University, Kaifeng, Henan, People's Republic of China
| | - Shuang-Yu Lv
- School of Medicine, Henan University, Kaifeng, Henan, People's Republic of China
| | - Bianfei Yu
- Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, People's Republic of China
| | - Shuang Xu
- Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, People's Republic of China
| | - Jianmin Shen
- Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, People's Republic of China
| | - Tong Zhao
- Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, People's Republic of China
| | - Haixia Zhang
- Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, People's Republic of China
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28
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Møller P, Jensen DM, Christophersen DV, Kermanizadeh A, Jacobsen NR, Hemmingsen JG, Danielsen PH, Karottki DG, Roursgaard M, Cao Y, Jantzen K, Klingberg H, Hersoug LG, Loft S. Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2015; 56:97-110. [PMID: 25196723 DOI: 10.1002/em.21899] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 08/20/2014] [Accepted: 08/21/2014] [Indexed: 06/03/2023]
Abstract
Increased levels of oxidatively damaged DNA have been documented in studies of metal, metal oxide, carbon-based and ceramic engineered nanomaterials (ENMs). In particular, 8-oxo-7,8-dihydroguanine-2'-deoxyguanosine (8-oxodG) is widely assessed as a DNA nucleobase oxidation product, measured by chromatographic assays, antibody-based methods or the comet assay with DNA repair enzymes. However, spurious oxidation of DNA has been a problem in certain studies applying chromatographic assays, yielding high baseline levels of 8-oxodG. Antibody-based assays detect high 8-oxodG baseline levels, related to cross-reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations between exposure to ENMs and oxidized DNA in tissue than studies showing acceptable baseline levels (odds ratio = 12.1, 95% confidence interval: 1.2-124). Nevertheless, reliable studies indicate that intratracheal instillation of nanosized carbon black is associated with increased levels of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential.
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Affiliation(s)
- Peter Møller
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark
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29
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Yang L, Kuang H, Zhang W, Aguilar ZP, Xiong Y, Lai W, Xu H, Wei H. Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice. NANOSCALE 2015; 7:625-636. [PMID: 25423473 DOI: 10.1039/c4nr05061d] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
In spite of the immense benefits from iron oxide magnetic nanoparticles (IOMNs), there is scanty information regarding their metabolic activities and toxicity in vivo. In this study, we investigated the size dependent in vivo biodistribution, toxicokinetics, and toxicity and gene expression changes of various sizes of carboxyl coated IOMNs (diameters of 10, 20, 30, and 40 nm). Our findings demonstrated that the various sizes of IOMNs accumulated primarily in the liver and spleen on the first day post-injection. Interestingly, size dependent biodistribution and transport were observed: the smallest IOMNs (10 nm) showed the highest uptake by the liver, whereas the largest IOMNs (40 nm) showed the highest uptake by the spleen. Moreover, the IOMNs with the smallest size (10 nm) were cleared faster from the liver and kidneys, but more readily entered the brain and the uterus. IOMNs with the largest size (40 nm) accumulated more readily but were easily eliminated in the spleen. However, the level of iron in the heart decreased in all IOMN exposed groups. In addition, blood biochemistry, hematological analyses and histological examination demonstrated that there was no apparent acute toxicity caused by IOMNs in mice. However, smaller IOMNs (10 nm and 20 nm) more effectively changed the expression level of sensitive genes related to oxidant stress, iron transport, metabolic process, apoptosis, and others.
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Affiliation(s)
- Lin Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
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30
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31
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Tmejova K, Hynek D, Kopel P, Krizkova S, Blazkova I, Trnkova L, Adam V, Kizek R. Study of metallothionein–quantum dots interactions. Colloids Surf B Biointerfaces 2014; 117:534-7. [DOI: 10.1016/j.colsurfb.2014.03.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 02/12/2014] [Accepted: 03/05/2014] [Indexed: 10/25/2022]
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32
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Yang Y, Zhao T, Cheng T, Shen J, Liu X, Yu B, Lv S, Zhang H. Hepatotoxicity induced by ZnO quantum dots in mice. RSC Adv 2014. [DOI: 10.1039/c3ra46583g] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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33
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Benetti F, Bregoli L, Olivato I, Sabbioni E. Effects of metal(loid)-based nanomaterials on essential element homeostasis: The central role of nanometallomics for nanotoxicology. Metallomics 2014; 6:729-47. [DOI: 10.1039/c3mt00167a] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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34
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Aye M, Di Giorgio C, Mekaouche M, Steinberg JG, Brerro-Saby C, Barthélémy P, De Méo M, Jammes Y. Genotoxicity of intraperitoneal injection of lipoamphiphile CdSe/ZnS quantum dots in rats. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2013; 758:48-55. [DOI: 10.1016/j.mrgentox.2013.09.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 09/07/2013] [Accepted: 09/12/2013] [Indexed: 11/15/2022]
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35
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Tang Y, Han S, Liu H, Chen X, Huang L, Li X, Zhang J. The role of surface chemistry in determining in vivo biodistribution and toxicity of CdSe/ZnS core-shell quantum dots. Biomaterials 2013; 34:8741-55. [PMID: 23932294 DOI: 10.1016/j.biomaterials.2013.07.087] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 07/25/2013] [Indexed: 10/26/2022]
Abstract
To examine the effect of surface chemistry and surface charge on in vivo biodistribution and toxicity of CdSe/ZnS core-shell quantum dots (QDs), QDs with positive, negative, or PEG coating are used in this study for in vivo evaluation in a mouse model. The results suggest that QDs coated with cationic polydiallyldimethylammonium chloride (PDDA) preferentially deposit in the lung other than in the liver, while the negative and PEGylated QDs render abundant accumulation in the liver. At higher doses positive QDs with PDDA coating show severe acute toxicity due to pulmonary embolism. Independent of their surface coatings, all QDs cause injuries in specific tissues like liver, spleen, lung, and kidney, after acute and long-term exposure, and the degree of injuries is dominated by their surface properties. For the positively charged QDs, the acute phase toxicity is primarily contributed by the coating material PDDA, while coating on QDs may amplify both in vitro and in vivo toxicity of PDDA. PEGylated QDs display the slightest chronic injuries in the long-term toxicity examination in comparison to positive or negative ones.
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Affiliation(s)
- Yuan Tang
- Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China
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36
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Ladhar C, Geffroy B, Cambier S, Treguer-Delapierre M, Durand E, Brèthes D, Bourdineaud JP. Impact of dietary cadmium sulphide nanoparticles on Danio rerio zebrafish at very low contamination pressure. Nanotoxicology 2013; 8:676-85. [PMID: 23883150 DOI: 10.3109/17435390.2013.822116] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
To address the impact of cadmium sulphide nanoparticles (CdSNPs) of two different sizes (8 and 50 nm), Danio rerio zebrafish were dietary exposed to very low doses: 100 or 40 ng CdSNPs/day/g body weight for 36 or 60 days, respectively. The results obtained using RAPD-PCR genotoxicity test showed genomic alteration since the number of hybridisation sites of the RAPD probes was significantly modified after CdSNPs exposure. In addition, selected stress response genes were either repressed or upregulated in tissues of CdSNPs-exposed fish. Mitochondrial dysfunction was also caused by the presence of CdSNPs in food. Cadmium accumulation in fish tissues (brain and muscles) could only be observed after 60 days of exposure. CdSNPs toxicity was dependent on their size and concentration.
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Affiliation(s)
- Chiraz Ladhar
- University of Bordeaux, CNRS, UMR 5805, Arcachon Marine Station , Place du Dr Peyneau, 33120 Arcachon , France
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37
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Møller P, Danielsen PH, Jantzen K, Roursgaard M, Loft S. Oxidatively damaged DNA in animals exposed to particles. Crit Rev Toxicol 2013; 43:96-118. [PMID: 23346980 DOI: 10.3109/10408444.2012.756456] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Exposure to combustion-derived particles, quartz and asbestos is associated with increased levels of oxidized and mutagenic DNA lesions. The aim of this survey was to critically assess the measurements of oxidatively damaged DNA as marker of particle-induced genotoxicity in animal tissues. Publications based on non-optimal assays of 8-oxo-7,8-dihydroguanine by antibodies and/or unrealistically high levels of 8-oxo-7,8-dihydroguanine (suggesting experimental problems due to spurious oxidation of DNA) reported more induction of DNA damage after exposure to particles than did the publications based on optimal methods. The majority of studies have used single intracavitary administration or inhalation with dose rates exceeding the pulmonary overload threshold, resulting in cytotoxicity and inflammation. It is unclear whether this is relevant for the much lower human exposure levels. Still, there was linear dose-response relationship for 8-oxo-7,8-dihydroguanine in lung tissue without obvious signs of a threshold. The dose-response function was also dependent on chemical composition and other characteristics of the administered particles, whereas dependence on species and strain could not be equivocally determined. Roles of cytotoxicity or inflammation for oxidatively induced DNA damage could not be documented or refuted. Studies on exposure to particles in the gastrointestinal tract showed consistently increased levels of 8-oxo-7,8-dihydroguanine in the liver. Collectively, there is evidence from animal experimental models that both pulmonary and gastrointestinal tract exposure to particles are associated with elevated levels of oxidatively damaged DNA in the lung and internal organs. However, there is a paucity of studies on pulmonary exposure to low doses of particles that are relevant for hazard/risk assessment.
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Affiliation(s)
- Peter Møller
- Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
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38
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Luo YH, Wu SB, Wei YH, Chen YC, Tsai MH, Ho CC, Lin SY, Yang CS, Lin P. Cadmium-Based Quantum Dot Induced Autophagy Formation for Cell Survival via Oxidative Stress. Chem Res Toxicol 2013; 26:662-73. [DOI: 10.1021/tx300455k] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Yueh-Hsia Luo
- Division of Environmental Health
and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China
| | - Shi-Bei Wu
- Department of Biochemistry and
Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan, Republic of China
| | - Yau-Huei Wei
- School of Medicine, Mackay Medical College, New Taipei City 252, Taiwan,
Republic of China
| | - Yu-Ching Chen
- Center
for Nanomedicine Research, National Health Research Institutes, Zhunan, Taiwan,
Republic of China
| | - Ming-Hsien Tsai
- Division of Environmental Health
and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China
| | - Chia-Chi Ho
- Division of Environmental Health
and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China
| | - Shu-Yi Lin
- Center
for Nanomedicine Research, National Health Research Institutes, Zhunan, Taiwan,
Republic of China
| | - Chung-Shi Yang
- Center
for Nanomedicine Research, National Health Research Institutes, Zhunan, Taiwan,
Republic of China
| | - Pinpin Lin
- Division of Environmental Health
and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China
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39
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Ho CC, Luo YH, Chuang TH, Yang CS, Ling YC, Lin P. Quantum dots induced monocyte chemotactic protein-1 expression via MyD88-dependent Toll-like receptor signaling pathways in macrophages. Toxicology 2013; 308:1-9. [PMID: 23499856 DOI: 10.1016/j.tox.2013.03.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 03/08/2013] [Accepted: 03/08/2013] [Indexed: 12/14/2022]
Abstract
Quantum dots (QDs) are nano-sized semiconductors. Previously, intratracheal instillation of QD705s induces persistent inflammation in mouse lungs. In our present study, QD705-COOH and QD705-PEG activated NF-κB and increased monocyte chemotactic protein-1 (MCP-1) expression in macrophages RAW264.7 via MyD88 dependent Toll-like receptor (TLR) signaling pathways. MyD88 is an adapter protein for most TLRs to activate NF-κB. Silencing expression of MyD88 or p65 with siRNA or co-treatment with a NF-κB inhibitor tremendously abolished QD705s-induced NF-κB activity and MCP-1 expression. The involved TLRs might locate either on the cell surface or inside of cells. Co-treatment with a TLR4 inhibitor completely prevented MCP-1 induction by QD705-PEG. Nevertheless, QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented MCP-1 induction. These findings indicate that, depending on their surface modification, OD705s activate MyD88 dependent-TLRs at the surface or inside of the cells, which is an important mechanism for nanoparticles-induced inflammatory responses. But other MyD88-independent pathways may also involve in these responses.
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Affiliation(s)
- Chia-Chi Ho
- Institute of NanoEngineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, ROC
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40
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Loginova YF, Kazachkina NI, Zherdeva VV, Rusanov AL, Shirmanova MV, Zagaynova EV, Sergeeva EA, Dezhurov SV, Wakstein MS, Savitsky AP. Biodistribution of intact fluorescent CdSe/CdS/ZnS quantum dots coated by mercaptopropionic acid after intravenous injection into mice. JOURNAL OF BIOPHOTONICS 2012; 5:848-859. [PMID: 23109471 DOI: 10.1002/jbio.201200124] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2012] [Revised: 09/21/2012] [Accepted: 09/22/2012] [Indexed: 06/01/2023]
Abstract
Semiconductor quantum dots (QD) have been widely used for fluorescent bioimaging. However their biosafety has attracted increasing attention, since the data about their in vivo behavior in biological systems are still limited. In this paper we have investigated the short- and long-term biodistribution of intact fluorescent CdSe/CdS/ZnS QD coated by 3-mercaptopropionic acid in mice. The results showed that intravenously injected QD accumulated mainly in the lungs, liver and spleen and were retained in these tissues for over 22 days. QD caused signs of acute toxicity in mice including death. The investigated QD possibly caused vascular thrombosis. The results of a toxicological assay indicated that some histopathological changes occurred in the lung tissue after the injection of QD. Our study highlights the need for careful evaluation of QD safety before their use in biological applications.
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Affiliation(s)
- Yana F Loginova
- A N Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia
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41
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Lin CH, Chang LW, Wei YH, Wu SB, Yang CS, Chang WH, Chen YC, Lin PP. Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te-based quantum dot 705 toxicity in vivo. Kaohsiung J Med Sci 2012; 28:S53-62. [PMID: 22871604 DOI: 10.1016/j.kjms.2012.05.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Accepted: 11/04/2011] [Indexed: 10/28/2022] Open
Abstract
The safety of quantum dots (QDs) 705 was evaluated in this study. Mice were treated with QD705 (intravenous) at a single dose of (40 pmol) for 4, 12, 16, and 24 weeks. Effects of QD705 on kidneys were examined. While there was a lack of histopathology, reduction in renal functions was detected at 16 weeks. Electron microscopic examination revealed alterations in proximal convoluted tubule (PCT) cell mitochondria at even much earlier time, including disorientation and reduction of mitochondrial number (early change), mitochondrial swelling, and later compensatory mitochondrial hypertrophy (enlargement mitochondria: giant mitochondria with hyperplastic inner cristae) as well as mitochondrial hyperplasia (increase in mitochondrial biogenesis and numbers) were observed. Such changes probably represent compensatory attempts of the mitochondria for functional loss or reduction of mitochondria in QD705 treated animals. Moreover, degeneration of mitochondria (myelin-figure and cytoplasmic membranous body formation) and degradation of cytoplasmic materials (isolated cytoplasmic pockets of degenerated materials and focal cytoplasmic degradation) also occurred in later time points (16-24 weeks). Such mitochondrial changes were not identical with those induced by pure cadmium. Taken together, we suggest that mitochondria appeared to be the target of QD705 toxicity and specific mitochondrial markers may be useful parameters for toxicity assessments of QDs or other metal-based nanomaterials.
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Affiliation(s)
- Chia-Hua Lin
- Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan
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42
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McConnachie LA, White CC, Botta D, Zadworny ME, Cox DP, Beyer RP, Hu X, Eaton DL, Gao X, Kavanagh TJ. Heme oxygenase expression as a biomarker of exposure to amphiphilic polymer-coated CdSe/ZnS quantum dots. Nanotoxicology 2012; 7:181-91. [PMID: 22264017 DOI: 10.3109/17435390.2011.648224] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Because of their unique optical properties, quantum dots (QDs) have become a preferred system for ultrasensitive detection and imaging. However, since QDs commonly contain Cd and other heavy metals, concerns have been raised regarding their toxicity. QDs are thus commonly synthesised with a ZnS cap structure and/or coated with polymeric stabilisers. We recently synthesised amphiphilic polymer-coated tri-n-octylphosphine oxide - poly(maleic anhydride-alt-1-tetradecene (TOPO-PMAT) QDs, which are highly stable in aqueous environments. The effects of these QDs on viability and stress response in five cell lines of mouse and human origins are reported here. Human and mouse macrophages and human kidney cells readily internalised these QDs, resulting in modest toxicity. TOPO-PMAT QD exposure was highly correlated with the induction of the stress response protein heme oxygenase-1 (HMOX1). Other stress biomarkers (glutamate cysteine ligase modifier subunit, NAD(P)H, necrosis) were only moderately affected. HMOX1 may thus be a useful biomarker of TOPO-QDOT QD exposure across cell types and species.
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Affiliation(s)
- Lisa A McConnachie
- Department of Environmental and Occupational Health Sciences, University of Washington , Seattle, WA 98195, USA
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