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Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 19402

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Special Issue Editors

Dr. Valeria De Matteis

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Guest Editor

Nanobiotechnology, Nanomedicine, and Nanobioelectronics Laboratory, Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento, via per Arnesano 16, 73100 Lecce, Italy
Interests: physics applied to biology; nanomaterials and toxicity; green nanomaterials; biophysics of cell membranes; biomaterials; silver and gold nanoparticles
Special Issues, Collections and Topics in MDPI journals

Dr. Mariafrancesca Cascione

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Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento, Via Monteroni, 73100 Lecce, Italy
Interests: cancer cells; atomic force microscopy; cell mechanical alteration
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Quaiser Saquib

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Department of Zoology, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia
Interests: cell biology; molecular toxicology; transcriptomics; genotoxicity; nanotoxicity

Special Issue Information

Dear Colleagues,

The wide use of nanoparticles in several fields due to their unique physicochemical properties has raised the problem of their toxicity. Despite their numerous advantages, many nano-scale inorganic materials are considered toxic due to the high surface-to-volume ratio that increases their interaction with biological systems. Therefore, it is crucial to study in detail the interaction mechanism of nanoparticles with different cellular compartments (plasma membrane, subcellular organelles, and nucleus). Furthermore, the distribution kinetics within living organisms and their possible accumulation in organs and tissues are also essential to outline a toxicological profile, specific for each kind of nanoparticle. Although several studies have already been carried out, the scientific community is working on the formulation of standard guidelines in order to regulate the use of nanoparticles in commercial products and for applications in nanomedicine (as therapeutic agents, drug carriers, or diagnostic agents). On the other side, in recent decades, emerging pollutants (new flame retardants, new phthalates, alternative bisphenols) have been used as additive chemicals in a several consumer products. Humans can be exposed to these pollutants through different routes, leading to their detection in bodily fluids. These harmful substances are linked to several human health ailments, e.g., disturbances in hormone levels, fecundability, neurodevelopment disorders, and adverse birth outcomes.

This Special Issue of the International Journal of Molecular Science entitled “Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms” aims to understand the toxic effects of different kinds of nanoparticles and emerging pollutants on cells and living organisms investigating the underlying mechanisms, disturbances in the biochemical pathways, and toxicogenomic changes. In addition, new techniques able to functionalize the surface of nanoparticles to reduce their adverse effects in vitro and in vivo are investigated.

Dr. Valeria De Matteis
Dr. Mariafrancesca Cascione
Prof. Dr. Quaiser Saquib
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nanoparticles
cytotoxicity
genotoxicity
nanomedicine
nanotoxicity
emerging pollutants
toxicogenomics
molecular toxicity
cell death

Published Papers (8 papers)

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Research

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21 pages, 5667 KiB

Open AccessArticle

Effectiveness of Nonfunctionalized Graphene Oxide Nanolayers as Nanomedicine against Colon, Cervical, and Breast Cancer Cells

by Mohammad Rafe Hatshan, Quaiser Saquib, Maqsood A. Siddiqui, Mohammad Faisal, Javed Ahmad, Abdulaziz A. Al-Khedhairy, Mohammed Rafi Shaik, Mujeeb Khan, Rizwan Wahab, Valeria De Matteis and Syed Farooq Adil

Int. J. Mol. Sci. 2023, 24(11), 9141; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24119141 - 23 May 2023

Viewed by 1555

Abstract

Recent studies in nanomedicine have intensively explored the prospective applications of surface-tailored graphene oxide (GO) as anticancer entity. However, the efficacy of nonfunctionalized graphene oxide nanolayers (GRO-NLs) as an anticancer agent is less explored. In this study, we report the synthesis of GRO-NLs and their in vitro anticancer potential in breast (MCF-7), colon (HT-29), and cervical (HeLa) cancer cells. GRO-NLs-treated HT-29, HeLa, and MCF-7 cells showed cytotoxicity in the MTT and NRU assays via defects in mitochondrial functions and lysosomal activity. HT-29, HeLa, and MCF-7 cells treated with GRO-NLs exhibited substantial elevations in ROS, disturbances of the mitochondrial membrane potential, an influx of Ca²⁺, and apoptosis. The qPCR quantification showed the upregulation of caspase 3, caspase 9, bax, and SOD1 genes in GRO-NLs-treated cells. Western blotting showed the depletion of P21, P53, and CDC25C proteins in the above cancer cell lines after GRO-NLs treatment, indicating its function as a mutagen to induce mutation in the P53 gene, thereby affecting P53 protein and downstream effectors P21 and CDC25C. In addition, there may be a mechanism other than P53 mutation that controls P53 dysfunction. We conclude that nonfunctionalized GRO-NLs exhibit prospective biomedical application as a putative anticancer entity against colon, cervical, and breast cancers. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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14 pages, 2892 KiB

Open AccessArticle

The Size-Dependent Effects of Silver Nanoparticles on Germination, Early Seedling Development and Polar Metabolite Profile of Wheat (Triticum aestivum L.)

by Lesław Bernard Lahuta, Joanna Szablińska-Piernik, Karolina Stałanowska, Katarzyna Głowacka and Marcin Horbowicz

Int. J. Mol. Sci. 2022, 23(21), 13255; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113255 - 31 Oct 2022

Cited by 7 | Viewed by 1645

Abstract

The phytotoxicity of silver nanoparticles (Ag NPs) to plant seeds germination and seedlings development depends on nanoparticles properties and concentration, as well as plant species and stress tolerance degrees. In the present study, the effect of citrate-stabilized spherical Ag NPs (20 mg/L) in sizes of 10, 20, 40, 60, and 100 nm, on wheat grain germination, early seedlings development, and polar metabolite profile in 3-day-old seedlings were analyzed. Ag NPs, regardless of their sizes, did not affect the germination of wheat grains. However, the smaller nanoparticles (10 and 20 nm in size) decreased the growth of seedling roots. Although the concentrations of total polar metabolites in roots, coleoptile, and endosperm of seedlings were not affected by Ag NPs, significant re-arrangements of carbohydrates profiles in seedlings were noted. In roots and coleoptile of 3-day-old seedlings, the concentration of sucrose increased, which was accompanied by a decrease in glucose and fructose. The concentrations of most other polar metabolites (amino acids, organic acids, and phosphate) were not affected by Ag NPs. Thus, an unknown signal is released by small-sized Ag NPs that triggers affection of sugars metabolism and/or distribution. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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15 pages, 1898 KiB

Open AccessArticle

Model Study for Interaction of Sublethal Doses of Zinc Oxide Nanoparticles with Environmentally Beneficial Bacteria Bacillus thuringiensis and Bacillus megaterium

by Katarzyna Matyszczuk and Anna Krzepiłko

Int. J. Mol. Sci. 2022, 23(19), 11820; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911820 - 05 Oct 2022

Cited by 2 | Viewed by 1461

Abstract

Zinc oxide nanoparticles (ZnO NPs), due to their antibacterial effects, are commonly used in various branches of the economy and can affect rhizobacteria that promote plant growth. We describe the effect of ZnO NPs on two model bacteria strains, B. thuringiensis and B. megaterium, that play an important role in the environment. The MIC (minimum inhibitory concentration) value determined after 48 h of incubation with ZnO NPs was more than 1.6 mg/mL for both strains tested, while the MBC (minimum bactericidal concentration) was above 1.8 mg/mL. We tested the effect of ZnO NPs at concentrations below the MIC (0.8 mg/mL, 0.4 mg/mL and 0.2 mg/mL (equal to 50%, 25% and 12,5% MIC, respectively) in order to identify the mechanisms activated by Bacillus species in the presence of these nanoparticles. ZnO NPs in sublethal concentrations inhibited planktonic cell growth, stimulated endospore formation and reduced decolorization of Evans blue. The addition of ZnO NPs caused oxidative stress, measured using nitroblue tetrazolium (NBT), and reduced the activity of catalase. It was confirmed that zinc oxide nanoparticles in sublethal concentrations change metabolic processes in Bacillus bacteria that are important for their effects on the environment. B. thuringiensis after treatment with ZnO NPs decreased indole acetic acid (IAA) production and increased biofilm formation, whereas B. megaterium decreased IAA production but, inversely, increased biofilm formation. Comparison of different Bacillus species in a single experiment made it possible to better understand the mechanisms of toxicity of zinc oxide nanoparticles and the individual reactions of closely related bacterial species. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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23 pages, 3911 KiB

Open AccessArticle

Effect of Silver Nanoparticles on the In Vitro Regeneration, Biochemical, Genetic, and Phenotype Variation in Adventitious Shoots Produced from Leaf Explants in Chrysanthemum

by Alicja Tymoszuk and Dariusz Kulus

Int. J. Mol. Sci. 2022, 23(13), 7406; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137406 - 03 Jul 2022

Cited by 8 | Viewed by 1982

Abstract

Novel and unique properties of nanomaterials, which are not apparent in larger-size forms of the same material, encourage the undertaking of studies exploring the multifaced effects of nanomaterials on plants. The results of such studies are not only scientifically relevant but, additionally, can be implemented to plant production and/or breeding. This study aimed to verify the applicability of silver nanoparticles (AgNPs) as a mutagen in chrysanthemum breeding. Chrysanthemum × grandiflorum (Ramat.) Kitam. ‘Lilac Wonder’ and ‘Richmond’ leaf explants were cultured on the modified MS medium supplemented with 0.6 mg·L⁻¹ 6-benzylaminopurine (BAP) and 2 mg·L⁻¹ indole-3-acetic acid (IAA) and treated with AgNPs (spherical; 20 nm in diameter size; 0, 50, and 100 mg·L⁻¹). AgNPs strongly suppressed the capability of leaf explants to form adventitious shoots and the efficiency of shoot regeneration. The content of primary and secondary metabolites (chlorophyll a, chlorophyll b, total chlorophylls, carotenoids, anthocyanins, phenolic compounds) and the activity of enzymatic antioxidants (superoxide dismutase and guaiacol peroxide) in leaf explants varied depending on the AgNPs treatment and age of culture. Phenotype variations of ex vitro cultivated chrysanthemums, covering the color and pigment content in the inflorescence, were detected in one 50 mg·L⁻¹ AgNPs-derived and five 100 mg·L⁻¹ AgNPs-derived ‘Lilac Wonder’ plants and were manifested as the color change from pink to burgundy-gold. However, no changes in inflorescence color/shape were found among AgNPs-treated ‘Richmond’ chrysanthemums. On the other hand, the stem height, number of leaves, and chlorophyll content in leaves varied depending on the AgNPs treatment and the cultivar analyzed. A significant effect of AgNPs on the genetic variation occurrence was found. A nearly two-fold higher share of polymorphic products, in both cultivars studied, was generated by RAPD markers than by SCoTs. To conclude, protocols using leaf explant treatment with AgNPs can be used as a novel breeding technique in chrysanthemum. However, the individual cultivars may differ in biochemical response, the efficiency of in vitro regeneration, genetic variation, and frequency of induced mutations in flowering plants. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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23 pages, 4778 KiB

Open AccessArticle

Lethality of Zinc Oxide Nanoparticles Surpasses Conventional Zinc Oxide via Oxidative Stress, Mitochondrial Damage and Calcium Overload: A Comparative Hepatotoxicity Study

by Xingyao Pei, Haiyang Jiang, Gang Xu, Cun Li, Daowen Li and Shusheng Tang

Int. J. Mol. Sci. 2022, 23(12), 6724; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126724 - 16 Jun 2022

Cited by 15 | Viewed by 2046

Abstract

Zinc oxide nanoparticles (ZnO NPs) with high bioavailability and excellent physicochemical properties are gradually becoming commonplace as a substitute for conventional ZnO materials. The present study aimed to investigate the hepatotoxicity mechanism of ZnO NPs and traditional non-nano ZnO particles, both in vivo and in vitro, and identify the differences in their toxic effects. The results showed that the extent and conditions of zinc ion release from ZnO NPs were inconsistent with those of ZnO. The RNA-seq results revealed that the expression quantity of differentially expressed genes (DEGs) and differentially expressed transcripts (DETs) affected by ZnO NPs was more than in ZnO, and the overall differences in genes or transcripts in the ZnO NPs group were more pronounced than in the ZnO group. Furthermore, the cell inactivation, oxidative stress, mitochondrial damage, and intracellular calcium overload induced by ZnO NPs were more serious than ZnO in HepG2 cells. Moreover, compared with traditional ZnO, the rat liver damage induced by ZnO NPs was more significant, with evidence of higher AST and ALT levels, weaker antioxidant capacity, and more serious histopathological damage (p < 0.05). In summary, the hepatotoxicity of ZnO NPs was more serious than that of conventional ZnO, which is helpful to understand the hepatotoxicity mechanism of Zn compounds in different states and improve the risk assessment of novel nano ZnO products in a variety of applications. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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16 pages, 3892 KiB

Open AccessArticle

Cyto-Genotoxic and Transcriptomic Alterations in Human Liver Cells by Tris (2-Ethylhexyl) Phosphate (TEHP): A Putative Hepatocarcinogen

by Quaiser Saquib, Abdullah M. Al-Salem, Maqsood A. Siddiqui, Sabiha M. Ansari, Xiaowei Zhang and Abdulaziz A. Al-Khedhairy

Int. J. Mol. Sci. 2022, 23(7), 3998; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073998 - 03 Apr 2022

Cited by 3 | Viewed by 2386

Abstract

Tris (2-ethylhexyl) phosphate (TEHP) is an organophosphate flame retardant (OPFRs) which is extensively used as a plasticizer and has been detected in human body fluids. Contemporarily, toxicological studies on TEHP in human cells are very limited and there are few studies on its genotoxicity and cell death mechanism in human liver cells (HepG2). Herein, we find that HepG2 cells exposed to TEHP (100, 200, 400 µM) for 72 h reduced cell survival to 19.68%, 49.83%, 58.91% and 29.08%, 47.7% and 57.90%, measured by MTT and NRU assays. TEHP did not induce cytotoxicity at lower concentrations (5, 10, 25, 50 µM) after 24 h and 48 h of exposure. Flow cytometric analysis of TEHP-treated cells elevated intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca⁺⁺ influx and esterase levels, leading to mitochondrial dysfunction (ΔΨm). DNA damage analysis by comet assay showed 4.67, 9.35, 13.78-fold greater OTM values in TEHP (100, 200, 400 µM)-treated cells. Cell cycle analysis exhibited 23.1%, 29.6%, and 50.8% of cells in SubG1 apoptotic phase after TEHP (100, 200 and 400 μM) treatment. Immunofluorescence data affirmed the activation of P53, caspase 3 and 9 proteins in TEHP-treated cells. In qPCR array of 84 genes, HepG2 cells treated with TEHP (100 µM, 72 h) upregulated 10 genes and downregulated 4 genes belonging to a human cancer pathway. Our novel data categorically indicate that TEHP is an oxidative stressor and carcinogenic entity, which exaggerates mitochondrial functions to induce cyto- and genotoxicity and cell death, implying its hepatotoxic features. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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16 pages, 2002 KiB

Open AccessArticle

Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids

by Marko R. Antonijević, Edina H. Avdović, Dušica M. Simijonović, Žiko B. Milanović, Ana D. Amić and Zoran S. Marković

Int. J. Mol. Sci. 2022, 23(1), 490; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010490 - 01 Jan 2022

Cited by 8 | Viewed by 1644

Abstract

Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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Review

Jump to: Research

16 pages, 1274 KiB

Open AccessReview

Nanoplastic Impact on the Gut-Brain Axis: Current Knowledge and Future Directions

by Wojciech Grodzicki, Katarzyna Dziendzikowska, Joanna Gromadzka-Ostrowska and Marcin Kruszewski

Int. J. Mol. Sci. 2021, 22(23), 12795; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312795 - 26 Nov 2021

Cited by 17 | Viewed by 5341

Abstract

The widespread usage of plastic places a significant burden on the environment and impacts numerous aquatic and terrestrial species. Humans in particular can be affected by plastic pollution, predominantly via inhalation and ingestion, as well as trophic transfer along the food chain. Under natural conditions synthetic materials undergo degradation into micro- and nanoparticles, especially prone to interact with biological systems. Organisms exposed to nanoplastic accumulate it in multiple tissues, including the gut and the brain. This phenomenon raises a question about the impact of nanoparticulate plastics on the communication pathways between these organs. The aim of this review is to explore an unsettling possibility of the influence of nanoplastic on the gut-brain axis and provide a comprehensive summary of available data regarding this subject. The scarce but consistent evidence shows that exposure to plastic nanoparticles can indeed affect both the digestive and the nervous system. Reported outcomes include microbiota alterations, intestinal barrier permeability, oxidative stress, inflammation, neurotoxicity and behavioral disturbances. Taking into consideration these alarming observations and the ubiquitous presence of plastics in human environment, more research is urgently needed in order to identify any potential threats that nanoplastic exposure can pose to the functioning of the gut-brain axis. Full article

(This article belongs to the Special Issue Toxicology Assessment of Nanoparticles and Emerging Pollutants on Cell Models and Living Organisms)

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