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Advances in Nanotoxicology: Health and Safety
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Advances in Nanotoxicology: Health and Safety

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: 13 June 2025 | Viewed by 9418

Special Issue Editors

Prof. Dr. Natalia Krasteva

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Guest Editor
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria
Interests: nanotoxicology; pharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Milena Georgieva

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Guest Editor
Laboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology "Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Interests: genetics; epigenetics; nanomaterials; nanomedicine; nanotechnology; nanoparticles; graphene; nanotoxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit an article to our Special Issue entitled “Advances in Nanotoxicology: Health and Safety”. Nanotoxicology has emerged as a prominent field within toxicology, driven by the urgent need to assess the safety of engineered nanomaterials for both human health and the environment. With the rapid integration of nanoscale materials into various aspects of daily life, such as cosmetics, food packaging, drug delivery systems, therapeutics, and biosensors, the number of individuals exposed to nanomaterials continues to rise. While nanoparticles offer significant benefits and advancements in preventing and treating various disorders, concerns have grown regarding their potential risks to human health and the environment. Consequently, nanotoxicology studies initially focused on understanding the dose–response relationship between nanomaterials and their toxicity using in vitro cell models. Extensive research has evaluated the physicochemical properties of nanomaterials, contributing to the definition of nanotoxicity. However, despite these efforts, there remains a lack of clarity and conflicting data regarding the cytotoxicity and biological fate of identical nanoparticles. This uncertainty suggests that we often fail to identify and control the relevant parameters that determine the toxicity of nanoparticles, both in vitro and in vivo. Achieving a comprehensive understanding of the toxicological impact of nanoparticles necessitates a consideration of the relevant factors and an understanding of nanoparticle interactions with biological systems at the molecular level. This knowledge can enable us to predict and mitigate the potential toxicity associated with novel nanomaterials, facilitating the design of safe, reliable, and efficient nanoparticles for biomedical applications.

This Special Issue aims to compile articles that assess the potential effects of emerging nanomaterials on the environment, evaluate their impact on human health, and elucidate the toxic mechanisms induced by nanoparticles. A comprehensive understanding of the pathophysiological mechanisms triggered by these advanced materials can be achieved by presenting data that consider both nanomaterials' advantages and their adverse effects. Ultimately, this knowledge may contribute to significant advancements in the field of nanomedicine. Submissions focusing on results obtained from preclinical studies or clinical trials are welcomed, as they will provide valuable insights into the potential benefits and risks associated with using nanomaterials in various contexts.

In this Special Issue, original research articles and reviews are welcomed. Research areas may include (but are not limited to) the following:

  • Environmental factors as triggers of mechanisms of systemic toxicities;
  • In vitro and in vivo experimental models for the evaluation of oxidative stress, DNA, and subcellular damages in pathogenesis of nanoparticle-induced toxicities;
  • Role of nanomaterials in medical diagnostics and therapeutics;
  • The evaluation of systemic toxicities and mechanism of toxicities induced by nanosized biomaterials;
  • Role of natural compounds in prevention and treatment of nanoparticle-induced toxicities;
  • Nanoformulation of food ingredients and their safety for human health;
  • Nanoparticles as anti-inflammatory and antioxidant agents;
  • Nanomedicine in clinical trials.

Prof. Dr. Natalia Krasteva
Prof. Dr. Milena Georgieva
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. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • advanced nanomaterials
  • mechanism of nanotoxicity
  • nanoformulations as drug delivery systems
  • nanomedicine in cancer therapy
  • environmental toxicity of nanomaterials

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Published Papers (5 papers)

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Research

20 pages, 3130 KiB  
Article
Skin Sensitization Potential of Sensitizers in the Presence of Metal Oxide Nanoparticles In Vitro
by Claudia Meindl, Kristin Öhlinger, Verena Zrim, Jennifer Ober, Ramona Jeitler, Eva Roblegg and Eleonore Fröhlich
Nanomaterials 2024, 14(22), 1811; https://doi.org/10.3390/nano14221811 - 12 Nov 2024
Viewed by 977
Abstract
Silica (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) nanoparticles (NPs) are widely used in dermal products. Their skin sensitization potential, especially their effects in combination with known sensitizers, is poorly studied in vitro and their sensitization inconsistently reported [...] Read more.
Silica (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) nanoparticles (NPs) are widely used in dermal products. Their skin sensitization potential, especially their effects in combination with known sensitizers, is poorly studied in vitro and their sensitization inconsistently reported in animal studies. In this study, cellular assays were used to identify different steps of sensitization, the activation of keratinocytes and dendritic cells, when cells were exposed to these NPs in the absence and presence of sensitizers. Cellular systems included HaCaT keratinocytes and U937 (U-SENS™) alone, as well as different co-culture systems of THP-1 cells with HaCaT cells (COCAT) and with primary keratinocytes. The effect of NPs differed between co-cultures and U-SENS™, whereas co-cultures with either primary keratinocytes or HaCaT cells responded similarly. Pre-exposure to ZnO NPs increased the U-SENS™ assay response to 2,4-dinitrochlorobenzene six-fold. The COCAT increase was maximally four-fold for the combination of SiO2 and trans cinnamaldehyde. When the THP-1 cells were separated from the keratinocytes by a membrane, the response of the co-culture system was more similar to U-SENS™. The direct contact with keratinocytes decreased the modulating effect of TiO2 and ZnO NPs but suggested an increase in response to sensitizers following dermal contact with SiO2 NPs. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology: Health and Safety)
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Figure 1

Figure 1
<p>Layout of the COCAT. Workflow of the routine assay is indicated in black, and adaptations for the co-exposure to NPs are indicated in brown.</p> Full article ">Figure 2
<p>HaCaT cells cultured in plastic wells (phase contrast) and on transwell membrane inserts (stained with HE). The cobblestone morphology is typical for the keratinocytes in plastic wells, and HaCaT cells form a stratified epithelium on membranes, similar to keratinocytes in normal skin. Scale bar: 100 µm.</p> Full article ">Figure 3
<p>Histograms of THP-1 cells stained with CD86 FITC and CD54 PE antibody. Cells gated based on the unstained controls are indicated for CD86 in red and for CD54 in green. Histograms of growth control (med) and solvent control (SC) (<b>a</b>), negative control (SDS) and positive control (DNCB) (<b>b</b>), are shown.</p> Full article ">Figure 3 Cont.
<p>Histograms of THP-1 cells stained with CD86 FITC and CD54 PE antibody. Cells gated based on the unstained controls are indicated for CD86 in red and for CD54 in green. Histograms of growth control (med) and solvent control (SC) (<b>a</b>), negative control (SDS) and positive control (DNCB) (<b>b</b>), are shown.</p> Full article ">Figure 4
<p>Cell viability is indicated as % of (medium or solvent) control. Viability was determined for trans cinnamaldehyde (TCA) in HaCaT keratinocytes (<b>a</b>). 2,4-dinitrochlorobenzene (DNCB), sodium dodecylsulfate (SDS) (<b>a</b>), SiO<sub>2</sub>, TiO<sub>2</sub>, and ZnO (<b>b</b>), were tested in HaCaT and primary keratinocytes.</p> Full article ">Figure 5
<p>Expression of CD86 by U937 cells in the U-Sens™ Assay after exposure to the NPs in combination with 2,4-dinitrochlorobenzene (DNCB) and trans cinnamaldehyde (TCA) as positive control (PC). The expression is normalized to CD86 expression induced by the sensitizer alone. Significant changes (<span class="html-italic">p</span> &lt; 0.05) are indicated by an asterisk.</p> Full article ">Figure 6
<p>CD86 and CD54 expression of THP-1 cells when HaCaT cells were exposed to NPs prior to contact with the positive controls (PCs), 2,4-dinitrochlorobenzene (DNCB, (<b>a</b>)) and trans cinnamaldehyde (TCA, (<b>b</b>)). Significant changes (<span class="html-italic">p</span> &lt; 0.05) are indicated by an asterisk.</p> Full article ">Figure 7
<p>CD86 expression of THP-1 cells in the COCAT_primary keratinocyte when primary keratinocytes were exposed to NPs prior to contact with the sensitizer (positive control) 2,4-dinitrochlorobenzene (DNCB). Significant changes are indicated by an asterisk (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 8
<p>CD86 and CD54 expression of THP-1 cells after exposure to NPs in the COCAT_transwell assay followed by sensitizer 2,4-dinitrochlorobenzene (DNCB). Significant changes are indicated by an asterisk (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">
22 pages, 2514 KiB  
Article
Specialized Pro-Resolving Lipid Mediators Distinctly Modulate Silver Nanoparticle-Induced Pulmonary Inflammation in Healthy and Metabolic Syndrome Mouse Models
by Arjun Pitchai, Akshada Shinde, Jenna N. Swihart, Kiley Robison and Jonathan H. Shannahan
Nanomaterials 2024, 14(20), 1642; https://doi.org/10.3390/nano14201642 - 13 Oct 2024
Viewed by 1217
Abstract
Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared [...] Read more.
Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared to a healthy mouse model, a mouse model of MetS exhibited increased pulmonary inflammation 24 h after exposure to AgNPs. This exacerbated response was associated with decreases in pulmonary levels of specific specialized pro-resolving mediators (SPMs). Supplementation with specific SPMs that are known to be dysregulated in MetS may alter particulate-induced inflammatory responses and be useful in treatment strategies. Our current study hypothesized that administration of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1) following AgNP exposure will differentially regulate inflammatory responses. To examine this hypothesis, healthy and MetS mouse models were exposed to either a vehicle (control) or 50 μg of 20 nm AgNPs via oropharyngeal aspiration. They were then treated 24 h post-exposure with either a vehicle (control) or 400 ng of RvE1, PD1, or MaR1 via oropharyngeal aspiration. Endpoints of pulmonary inflammation and toxicity were evaluated three days following AgNP exposure. MetS mice that were exposed to AgNPs and received PBS treatment exhibited significantly exacerbated pulmonary inflammatory responses compared to healthy mice. In mice exposed to AgNPs and treated with RvE1, neutrophil infiltration was reduced in healthy mice and the exacerbated neutrophil levels were decreased in the MetS model. This decreased neutrophilia was associated with decreases in proinflammatory cytokines’ gene and protein expression. Healthy mice treated with PD1 did not demonstrate alterations in AgNP-induced neutrophil levels compared to mice not receiving treat; however, exacerbated neutrophilia was reduced in the MetS model. These PD1 alterations were associated with decreases in proinflammatory cytokines, as well as elevated interleukin-10 (IL-10). Both mouse models receiving MaR1 treatment demonstrated reductions in AgNP-induced neutrophil influx. MaR1 treatment was associated with decreases in proinflammatory cytokines in both models and increases in the resolution inflammatory cytokine IL-10 in both models, which were enhanced in MetS mice. Inflammatory responses to particulate exposure may be treated using specific SPMs, some of which may benefit susceptible subpopulations. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology: Health and Safety)
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Figure 1

Figure 1
<p>Experiment design timeline. Mice were fed a healthy or high-fat western diet for 14 weeks and exposed to either water (control) or AgNPs (50 µg) via oropharyngeal aspiration; 24 h post-exposure, mice were treated with saline (control) or 400 ng of a lipid resolution mediator (RvE1, PD1, or MaR1) via oropharyngeal aspiration. Endpoints associated with inflammation and lipid metabolism were examined at 2 days following treatment.</p> Full article ">Figure 2
<p>Characterization of (<b>A</b>) body weight and serum levels of (<b>B</b>) high-density lipoprotein, (<b>C</b>) low-density lipoprotein, and (<b>D</b>) total cholesterol in healthy and MetS mouse models following 14 weeks of either a healthy or high-fat western diet (HFW diet) and 3 days after oropharyngeal aspiration exposure to pharmaceutical grade sterile water (vehicle) or 50 μg of AgNPs. Subsets of mice were treated with sterile saline (vehicle) or 400 ng of individual SPMs (RvE1, PD1, or MaR1) 24 h post-exposure. Values are expressed as mean ± S.E.M. # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 3
<p>AgNP exposure and modulation by distinct SPM treatment on BALF: (<b>A</b>) total protein, (<b>B</b>) total cell counts, (<b>C</b>) macrophage counts, and (<b>D</b>) neutrophil counts from healthy and MetS mice; 24 h following oropharyngeal aspiration of pharmaceutical grade sterile water (control) or 50 μg of AgNPs in sterile water, mice were treated via oropharyngeal aspiration with 400 ng of individual SPMs (RvE1, PD1, or MaR1) or sterile saline (vehicle). Endpoints were evaluated at 3 days post-AgNP exposure. Values are expressed as mean ± S.E.M. * AgNP exposure, # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 4
<p>AgNP exposure and modulation by distinct SPM treatment on the pulmonary gene expression of inflammatory factors including (<b>A</b>) (C-C motif) ligand 2 (CCL2), (<b>B</b>) interleukin-6 (IL-6), (<b>C</b>) chemokine (C-X-C motif) ligand 1 (CXCL1), (<b>D</b>) chemokine (C-X-C motif) ligand 2 (CXCL2), (<b>E</b>) tumor necrosis factor-α (TNF-α), and (<b>F</b>) interleukin-10 (IL-10) from healthy and MetS mice; 24 h following oropharyngeal aspiration of pharmaceutical grade sterile water (control) or 50 μg of AgNPs in sterile water, mice were treated via oropharyngeal aspiration with 400 ng of individual SPMs (RvE1, PD1, or MaR1) or sterile saline (vehicle). Endpoints were evaluated at 3 days post-AgNP exposure. Values are expressed as mean ± S.E.M. * AgNP exposure, # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 5
<p>AgNP exposure and modulation by distinct SPM treatment on pulmonary lipid metabolism gene expression, including (<b>A</b>) <span class="html-italic">phospholipase A2</span> (<span class="html-italic">iPLA2</span>), (<b>B</b>) <span class="html-italic">arachidonate 5-lipoxygenase</span> (<span class="html-italic">ALOX-5</span>), (<b>C</b>) <span class="html-italic">arachidonate 15-lipoxygenase</span> (<span class="html-italic">ALOX-15</span>), (<b>D</b>) <span class="html-italic">cyclooxygenase 2</span> (<span class="html-italic">COX 2</span>), and (<b>E</b>) <span class="html-italic">epoxide hydrolase 2</span> (<span class="html-italic">Ephx2</span>) from healthy and MetS mice; 24 h following oropharyngeal aspiration of pharmaceutical grade sterile water (control) or 50 μg of AgNPs in sterile water, mice were treated via oropharyngeal aspiration with 400 ng of individual SPMs or sterile saline (vehicle). Endpoints were evaluated at 3 days post-AgNP exposure. Values are expressed as mean ± S.E.M. * AgNP exposure, # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 6
<p>AgNP exposure and modulation by distinct SPM treatment on pulmonary lipid receptor gene expression including (<b>A</b>) the RvE1 receptor, <span class="html-italic">chemerin receptor 23</span> (<span class="html-italic">ChemR23</span>), (<b>B</b>) the PD1 receptor, <span class="html-italic">G protein-coupled receptor 37</span> (<span class="html-italic">GPR37</span>), and (<b>C</b>) the MaR1 receptor, <span class="html-italic">leucine-rich repeat containing G protein-coupled receptor 6</span> (<span class="html-italic">LGR6</span>) from healthy and MetS mice; 24 h following oropharyngeal aspiration of pharmaceutical grade sterile water (control) or 50 μg of AgNPs in sterile water, mice were treated via oropharyngeal aspiration with 400 ng of individual SPMs or sterile saline (vehicle). Endpoints were evaluated at 3 days post-AgNP exposures. Values are expressed as mean ± S.E.M. * AgNP exposure, # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 7
<p>AgNP exposure and modulation by distinct SPM treatment on BALF inflammatory cytokine and chemokine levels including (<b>A</b>) chemokine (C-X-C motif) ligand 2 (CXCL2), (<b>B</b>) interleukin-6 (IL-6), and (<b>C</b>) interleukin-10 (IL-10) from healthy and MetS mice; 24 h following oropharyngeal aspiration of pharmaceutical grade sterile water (control) or 50 μg of AgNPs in sterile water, mice were treated via oropharyngeal aspiration with 400 ng of individual SPMs or sterile saline (vehicle). Endpoints were evaluated at 3 days post-AgNP exposure. Values are expressed as mean ± S.E.M. * AgNP exposure, # disease model, and <span>$</span> treatment (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">
15 pages, 8158 KiB  
Article
Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study
by Tobias Haase, Antje Ludwig, Anke Stach, Azadeh Mohtashamdolatshahi, Ralf Hauptmann, Lars Mundhenk, Harald Kratz, Susanne Metzkow, Avan Kader, Christian Freise, Susanne Mueller, Nicola Stolzenburg, Patricia Radon, Maik Liebl, Frank Wiekhorst, Bernd Hamm, Matthias Taupitz and Jörg Schnorr
Nanomaterials 2024, 14(9), 773; https://doi.org/10.3390/nano14090773 - 28 Apr 2024
Cited by 1 | Viewed by 1745
Abstract
Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not [...] Read more.
Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not yet been studied. This study aimed to investigate the effect of multiple intravenous injections of VSOPs in atherosclerotic mice. Taurine-formulated VSOPs (VSOP-T) were repeatedly intravenously injected at 100 µmol Fe/kg in apolipoprotein E-deficient (ApoE KO) mice with diet-induced atherosclerosis. Angiographic imaging was carried out by in vivo MRI. Magnetic particle spectrometry was used to detect tissue VSOP content, and tissue iron content was quantified photometrically. Pathological changes in organs, atherosclerotic plaque development, and expression of hepatic iron-related proteins were evaluated. VSOP-T enabled the angiographic imaging of heart and blood vessels with a blood half-life of one hour. Repeated intravenous injection led to VSOP deposition and iron accumulation in the liver and spleen without affecting liver and spleen pathology, expression of hepatic iron metabolism proteins, serum lipids, or atherosclerotic lesion formation. Repeated injections of VSOP-T doses sufficient for MRA analyses had no significant effects on plaque burden, steatohepatitis, and iron homeostasis in atherosclerotic mice. These findings underscore the safety of VSOP-T and support its further development as a contrast agent and molecular imaging tool. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology: Health and Safety)
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Figure 1

Figure 1
<p>Dosing regimen and treatment schedule.</p> Full article ">Figure 2
<p>Size distribution is given by the number of particles of injected VSOP-T nanoparticles (<b>a</b>). Transmission electron microscopy (TEM) images show monocore structure and iron core sizes of approx. 6.5–7 nm for VSOPs (<b>b</b>).</p> Full article ">Figure 3
<p>Vascular imaging with VSOP-T in the ApoE KO mouse. 3D maximum intensity projection (MIP) of angiography (T1-weighted images) with VSOP-T in a dose of 100 µmol Fe/kg, under same view angle pre-VSOP administration and at the given time points (<b>a</b>). Signal intensity ratio (SNR) development over time (<b>b</b>). Ex vivo MR images of aortae showing iron accumulations in regions of atherosclerotic plaques 24 h after injection (white arrows) (<b>c</b>).</p> Full article ">Figure 4
<p>VSOP-T had no adverse hepatic or splenic effects. The characteristics of the hepatic lesions varied within the model; however, they were unaffected by the type of group. The hepatocytes of ApoE KO mice showed minimal (<b>A</b>,<b>B</b>) or severe vacuolization (<b>C</b>,<b>D</b>). In severely affected livers, the hepatocytes were variably sized, and the hypertrophied cells were predominately located centrolobular (<b>C</b>,<b>D</b>). The treatment with VSOP-T (<b>B</b>,<b>D</b>) had no effect on the hepatic phenotype. No differences were observed between the spleens of control (<b>E</b>) and VSOP-T-treated mice (<b>F</b>). Bars (<b>A</b>–<b>D</b>) = 50 µm. Bars (<b>E</b>,<b>F</b>) = 100 µm.</p> Full article ">Figure 5
<p>Visualization of iron in the hepatic sinusoidal lining cells. Compared to the liver of mice of the control group, the cytoplasm of hepatic sinusoidal lining cells of VSOP-T-treated mice stained intensively blue by Prussian blue staining (arrows). Bar = 50 µm.</p> Full article ">Figure 6
<p>Analyses of hepatic expressions of proteins relevant for iron transport and recycling by Western blot: ferritin (<b>a</b>), transferrin (<b>b</b>), and ferroportin (<b>c</b>). Left panels show the Western blot results of 10 control mice (C) versus 10 VSOP-T mice (VSOP-T) separated on two membranes. Amido black staining served as loading control (LC). The right panels show the respective signal intensity analysis.</p> Full article ">Figure 7
<p>Serum cholesterol (<b>a</b>) and triglyceride levels (<b>b</b>) of control and VSOP-T-treated ApoE KO mice on HFD (<span class="html-italic">n</span> = 10 mice per group). For comparison, serum cholesterol and triglyceride levels of C57Bl6/J mice on normal diet (<span class="html-italic">n</span> = 3) were included in the diagrams. Data are shown as mean ± SD and individual data points. *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 8
<p>Movat pentachrome staining and histological evaluation of vascular segments from (<b>a</b>) brachiocephalic trunk, (<b>b</b>) aortic arch, and (<b>c</b>) aortic root of control (circles) and VSOP-T-treated mice (squares) (<span class="html-italic">n</span> = 10 mice per group). Data are shown as mean ± SD and individual data points. Bar = 250 µm.</p> Full article ">Figure A1
<p>Relative body weight development of control and VSOP-T-treated mice over the period of 18 weeks on a Western-type diet. Means ± SD are shown (<span class="html-italic">n</span> = 10 animals per group).</p> Full article ">Figure A2
<p>Tissue sections were used for histological analysis of atherosclerotic vascular changes in the three different vascular segments: brachiocephalic trunk, aortic arch, and aortic root. Consecutive sections were cut through the entire vascular segments, and sections at the indicated positions (dotted lines, µm) were stained, scanned, and analyzed. Image modified from [<a href="#B33-nanomaterials-14-00773" class="html-bibr">33</a>].</p> Full article ">Figure A3
<p>Prussian blue staining of the mouse aortic root, 4 weeks after the last VSOP-T treatment showing no iron staining. Bar = 250 µm.</p> Full article ">
21 pages, 11621 KiB  
Article
In Vivo Assessment of Hepatic and Kidney Toxicity Induced by Silicon Quantum Dots in Mice
by Roxana-Elena Cristian, Cornel Balta, Hildegard Herman, Bogdan Trica, Beatrice G. Sbarcea, Anca Hermenean, Anca Dinischiotu and Miruna S. Stan
Nanomaterials 2024, 14(5), 457; https://doi.org/10.3390/nano14050457 - 1 Mar 2024
Cited by 1 | Viewed by 2167
Abstract
In the last decade, silicon-based quantum dots (SiQDs) have attracted the attention of researchers due to their unique properties for which they are used in medical applications and in vivo imaging. Detection of cytotoxic effects in vivo is essential for understanding the mechanisms [...] Read more.
In the last decade, silicon-based quantum dots (SiQDs) have attracted the attention of researchers due to their unique properties for which they are used in medical applications and in vivo imaging. Detection of cytotoxic effects in vivo is essential for understanding the mechanisms of toxicity, a mandatory step before their administration to human subjects. In this context, we aimed to evaluate the in vivo hepatic and renal acute toxicity of SiQDs obtained by laser ablation. The nanoparticles were administrated at different doses (0, 1, 10, and 100 mg of QDs/kg of body weight) by intravenous injection into the caudal vein of Swiss mice. After 1, 6, 24, and 72 h, the animals were euthanatized, and liver and kidney tissues were used in further toxicity tests. The time- and dose-dependent effects of SiQDs on the antioxidant defense system of mice liver and kidney were investigated by quantifying the activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) in correlation with the morphological changes and inflammatory status in the liver and kidneys. The results showed a decrease in the activities of antioxidant enzymes and histopathological changes, except for superoxide dismutase, in which no significant changes were registered compared with the control. Furthermore, the immunohistochemical expression of TNF-α was significant at doses over 10 mg of QDs/kg of body weight and were still evident at 72 h after administration. Our results showed that doses under 10 mg of SiQDs/kg of b.w. did not induce hepatic and renal toxicity, providing useful information for further clinical trials. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology: Health and Safety)
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Figure 1

Figure 1
<p>Morphological characterization of SiQDs by SEM (<b>a</b>) and TEM (<b>b</b>) investigations, with the spherical shape of QDs being marked by white dot circles. Hydrodynamic size, polydispersity index, and zeta potential (<b>c</b>) and absorbance and emission spectra (<b>d</b>) were measured for SiQDs dispersed in 0.9% NaCl solution.</p> Full article ">Figure 2
<p>Liver (<b>a</b>) and kidney (<b>b</b>) histopathology at 1 h, 6 h, 24 h, and 72 h after SiQDs administration (1, 10, and 100 mg/kg of b.w.) in mice. Tissue sections (5 µm) were stained with hematoxylin and eosin and examined by light microscopy. Legend of arrows: (<b>a</b>) 1—hepatocyte swelling, 2—inflammatory infiltrates; (<b>b</b>) 1—vascular congestion; 2—glomerular atrophy. Magnification of 10× for liver images and 20× for kidney images.</p> Full article ">Figure 2 Cont.
<p>Liver (<b>a</b>) and kidney (<b>b</b>) histopathology at 1 h, 6 h, 24 h, and 72 h after SiQDs administration (1, 10, and 100 mg/kg of b.w.) in mice. Tissue sections (5 µm) were stained with hematoxylin and eosin and examined by light microscopy. Legend of arrows: (<b>a</b>) 1—hepatocyte swelling, 2—inflammatory infiltrates; (<b>b</b>) 1—vascular congestion; 2—glomerular atrophy. Magnification of 10× for liver images and 20× for kidney images.</p> Full article ">Figure 3
<p>Immunohistochemistry for TNF-α in the liver (<b>a</b>) and kidneys (<b>b</b>) at 1 h, 6 h, 24 h, and 72 h after SiQDs administration (1, 10, and 100 mg/kg of b.w.) in mice. Magnification of 10× for liver images and 20× for kidney images.</p> Full article ">Figure 3 Cont.
<p>Immunohistochemistry for TNF-α in the liver (<b>a</b>) and kidneys (<b>b</b>) at 1 h, 6 h, 24 h, and 72 h after SiQDs administration (1, 10, and 100 mg/kg of b.w.) in mice. Magnification of 10× for liver images and 20× for kidney images.</p> Full article ">Figure 4
<p>Specific activities of SOD (<b>a</b>,<b>b</b>), CAT (<b>c</b>,<b>d</b>), Gred (<b>e</b>,<b>f</b>), GPx (<b>g</b>,<b>h</b>), and GST (<b>i</b>,<b>j</b>) in liver (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>) and kidney (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>) tissues collected at 1, 6, 24, and 72 h after SiQDs administration. Results are calculated as the mean ± SD (<span class="html-italic">n</span> = 5) and are represented relative to the control. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compare with the control.</p> Full article ">Figure 4 Cont.
<p>Specific activities of SOD (<b>a</b>,<b>b</b>), CAT (<b>c</b>,<b>d</b>), Gred (<b>e</b>,<b>f</b>), GPx (<b>g</b>,<b>h</b>), and GST (<b>i</b>,<b>j</b>) in liver (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>) and kidney (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>) tissues collected at 1, 6, 24, and 72 h after SiQDs administration. Results are calculated as the mean ± SD (<span class="html-italic">n</span> = 5) and are represented relative to the control. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compare with the control.</p> Full article ">Figure 5
<p>Levels of GSH (<b>a</b>,<b>b</b>) and MDA (<b>c</b>,<b>d</b>) in liver (<b>a</b>,<b>c</b>) and kidney (<b>b</b>,<b>d</b>) tissues collected at 1, 6, 24, and 72 h after SiQDs administration. Results are calculated as the mean ± SD (<span class="html-italic">n</span> = 5) and are represented relative to the control. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compare with the control.</p> Full article ">Figure 6
<p>Changes in the expression of proteins involved in the antioxidative defense response, apoptosis, and autophagy after SiQDs administration (100 mg/kg of b.w.) in mice. The analysis of Nrf-2, p53, Beclin-1, and LC-3 protein expression by Western blotting (<b>a</b>) was quantified in the liver (<b>b</b>,<b>d</b>,<b>f</b>,<b>g</b>) and kidney (<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>) tissues collected at 1, 6, 24, and 72 h after SiQDs administration. Results are calculated as the mean ± SD (<span class="html-italic">n</span> = 5) and are represented relative to the control. * <span class="html-italic">p</span> &lt; 0.05 compares with the control.</p> Full article ">Figure 6 Cont.
<p>Changes in the expression of proteins involved in the antioxidative defense response, apoptosis, and autophagy after SiQDs administration (100 mg/kg of b.w.) in mice. The analysis of Nrf-2, p53, Beclin-1, and LC-3 protein expression by Western blotting (<b>a</b>) was quantified in the liver (<b>b</b>,<b>d</b>,<b>f</b>,<b>g</b>) and kidney (<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>) tissues collected at 1, 6, 24, and 72 h after SiQDs administration. Results are calculated as the mean ± SD (<span class="html-italic">n</span> = 5) and are represented relative to the control. * <span class="html-italic">p</span> &lt; 0.05 compares with the control.</p> Full article ">Figure 7
<p>The levels of 8-OHdG (<b>a</b>) and global DNA methylation (<b>b</b>) as determined by the ELISA technique in the murine liver and kidney samples collected at 72 h after the administration of SiQDs (100 mg of QDs/kg of b.w.). Results are expressed as the mean ± SD (<span class="html-italic">n</span> = 5).</p> Full article ">Figure 8
<p>Changes in histone H4 in liver (<b>a</b>) and kidney (<b>b</b>) samples collected at 72 h after SiQDs administration (100 mg of QDs/kg of b.w.).</p> Full article ">Figure 8 Cont.
<p>Changes in histone H4 in liver (<b>a</b>) and kidney (<b>b</b>) samples collected at 72 h after SiQDs administration (100 mg of QDs/kg of b.w.).</p> Full article ">
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Article
Comprehensive Assessment of Graphene Oxide Nanoparticles: Effects on Liver Enzymes and Cardiovascular System in Animal Models and Skeletal Muscle Cells
by Milena Keremidarska-Markova, Iliyana Sazdova, Bilyana Ilieva, Milena Mishonova, Milena Shkodrova, Kamelia Hristova-Panusheva, Natalia Krasteva and Mariela Chichova
Nanomaterials 2024, 14(2), 188; https://doi.org/10.3390/nano14020188 - 13 Jan 2024
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Abstract
The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach [...] Read more.
The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach to assess the influence of GO and its polyethylene glycol-modified form (GO-PEG) under near-infrared (NIR) exposure on several biological aspects. We evaluated the contractility of isolated frog hearts, the activity of two rat liver enzymes–mitochondrial ATPase and diamine oxidase (DAO), and the production of reactive oxygen species (ROS) in C2C12 skeletal muscle cells following direct exposure to GO nanoparticles. The aim was to study the influence of GO nanoparticles at multiple levels—organ; cellular; and subcellular—to provide a broader understanding of their effects. Our data demonstrated that GO and GO-PEG negatively affect heart contractility in frogs, inducing stronger arrhythmic contractions. They increased ROS production in C2C12 myoblasts, whose effects diminished after NIR irradiation. Both nanoparticles in the rat liver significantly stimulated DAO activity, with amplification of this effect after NIR irradiation. GO did not uncouple intact rat liver mitochondria but caused a concentration-dependent decline in ATPase activity in freeze/thaw mitochondria. This multifaceted investigation provides crucial insights into GOs potential for diverse implications in biological systems. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology: Health and Safety)
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Figure 1

Figure 1
<p>Physiochemical properties of GO and GO-PEG NPs: (<b>a</b>) TEM analysis of GO and GO-PEG after sonication; (<b>b</b>) UV-Vis spectra of GO and GO-PEG.</p> Full article ">Figure 2
<p>Effects of GO and GO-PEG without and after NIR-irradiation on excised frog hearts. The maximal force of the heart contractions in control conditions (nanoparticle-free medium) is shown for comparison (time control, (<b>a</b>–<b>c</b>), open squares). Arrows point the solution changes (fresh Ringer solution for time control and the corresponding nanoparticle concentrations for experimental groups). Data are plotted as mean ± SEM (<span class="html-italic">n</span> = 6). Asterisks indicate significant difference between GO (<b>a</b>) and GO-PEG (<b>c</b>) versus the corresponding time control at each minute of the experiment. Carets indicate significant differences between GO-PEG (panel a) and GO-NIR (<b>b</b>) versus the corresponding time control: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; ^ &lt; 0.05, ^^ &lt; 0.01, ^^^ &lt; 0.001. The square brackets represent the time interval to which the observed significant deference refers.</p> Full article ">Figure 3
<p>Representative original record of excised frog heart contractions at control conditions and after application of increasing concentrations of nanoparticles. Circles point observed deviations in excitability of the cardiac muscle.</p> Full article ">Figure 4
<p>Effects of NIR irradiation of GO and GO-PEG nanoparticles on ROS levels. Data are presented as mean ± SEM of two independent experiments. Carets indicate significant differences for GO-NIR from the control: ^ <span class="html-italic">p</span> &lt; 0.05, ^^ <span class="html-italic">p</span> &lt; 0.01, ^^^ <span class="html-italic">p</span> &lt; 0.001. Sharps indicate significant differences for GO-PEG-NIR from GO-PEG: <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05.</p> Full article ">Figure 5
<p>Effects of graphene oxide (GO) (<b>a</b>) nanoparticles and irradiated GO nanoparticles (GO-NIR) (<b>b</b>) on ATPase activity in both intact and 2.4-dinitrophenol (DNP)-uncoupled mitochondria The reactions were started by adding 80 µL of mitochondrial suspension (protein 7.22 mg/sample and 6.64 mg/sample for GO and GO-NIR nanoparticles, respectively) and conducted for 600 s as described in the Materials and Methods section. The data presents curves registered during a single experiment with GO and GO-NIR nanoparticles, respectively.</p> Full article ">Figure 6
<p>Effects of GO and GO-NIR nanoparticles on ATPase activity of freeze-thawed mitochondria. ATPase activity values were calculated as percentages of the activity measured under control conditions (nanoparticle-free assay media). Data are plotted as mean ± SEM of six independent experiments (three parallel samples per group per experiment). Asterisks and carets indicate significant differences from the control: ** <span class="html-italic">p</span> &lt; 0.01 (for GO), ^^ <span class="html-italic">p</span> &lt; 0.01 (for GO-NIR).</p> Full article ">Figure 7
<p>Effect of GO and PEG-modified (GO-PEG) nanoparticles on DAO activity. DAO activity values were calculated as percentages of the enzyme activity measured under control conditions (nanoparticles-free media). Data are presented as mean ± SEM of six independent experiments. Asterisks and carets indicate significant differences from the control: * <span class="html-italic">p</span> &lt; 0.05 (for GO); ^ <span class="html-italic">p</span> &lt; 0.05, ^^ <span class="html-italic">p</span> &lt; 0.01 (for GO-PEG).</p> Full article ">Figure 8
<p>Effects of NIR irradiation of GO (<b>a</b>) and GO-PEG (<b>b</b>) nanoparticles on DAO activity. DAO activity values were calculated as a percentage of the enzyme activity measured under control conditions. Data are presented as mean ± SEM of six (seven for GO-NIR) independent experiments. Asterisks and carets indicate significant differences from the respective controls: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 (for GO and GO-PEG); ^ <span class="html-italic">p</span> &lt; 0.05, ^^ <span class="html-italic">p</span> &lt; 0.01, ^^^ <span class="html-italic">p</span> &lt; 0.001 (for GO-NIR and GO-PEG-NIR). Sharps indicate significant differences for GO-NIR and GO-PEG-NIR from GO and GO-PEG, respectively: <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">
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