Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 15218

Special Issue Editor


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Guest Editor
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
Interests: nanomaterials; tumor therapy; theranostics; antibacteria; biomedical effects and nanosafety; photothermal therapy; photodynamic therapy

Special Issue Information

Dear Colleagues,

With the rapid development of nanotechnology, metal nanoparticles and metal oxide nanoparticles have been applied in various fields, such as the food industry, the medical system and chemical engineering, because of their unique properties. However, with the large-scale preparation and wide application of nanomaterials, its potential harm to the environment and human beings has attracted more and more attention. Therefore, toxicity assessment is an essential and blossoming field, which mainly focuses on investigating the potential adverse effects of nanoparticles and their potential toxicity mechanisms. The systematic assessment of the toxicity of metal nanoparticles and metal oxide nanoparticles and their mechanisms can not only protect human health and the environment but can also help maximize the safe application of nanomaterials in various fields.

We invite authors to contribute original research articles or comprehensive review articles covering the toxicological assessment of metal nanoparticles, such as Au and Ag, and metal oxide nanoparticles, such as TiO2, ZnO, CeO2, MoOx, Fe2O3, and CuOx, on the human body and the environment.

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

  • Toxicity and ecological effects of metal nanoparticles and metal oxide nanoparticles
  • Environmental and health risk assessment of metal nanoparticles and metal oxide nanoparticles
  • The degradation technology of nanoparticle toxicity.
  • The toxic mechanism of metal nanoparticles and metal oxide nanoparticles.

We look forward to receiving your contributions.

Dr. Wenyan Yin
Guest Editor

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Keywords

  • metal nanoparticles
  • metal oxide nanoparticles
  • risk assessment
  • antibacterial
  • toxic mechanism
  • toxicity
  • ecotoxicity
  • genotoxicity

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Published Papers (6 papers)

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Research

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19 pages, 6802 KiB  
Article
Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes
by Tania Hernández-Jiménez, Pedro Cruz-Nova, Alejandra Ancira-Cortez, Brenda Gibbens-Bandala, Nancy Lara-Almazán, Blanca Ocampo-García, Clara Santos-Cuevas, Enrique Morales-Avila and Guillermina Ferro-Flores
Nanomaterials 2022, 12(23), 4181; https://doi.org/10.3390/nano12234181 - 25 Nov 2022
Cited by 10 | Viewed by 2024
Abstract
The fibroblast activation protein (FAP) is heavily expressed in fibroblasts associated with the tumor microenvironment, while the prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of malignant angiogenic processes. Previously, we reported that [177Lu]lutetium sesquioxide-iFAP/iPSMA nanoparticles ([177Lu]Lu−iFAP/iPSMA) inhibit [...] Read more.
The fibroblast activation protein (FAP) is heavily expressed in fibroblasts associated with the tumor microenvironment, while the prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of malignant angiogenic processes. Previously, we reported that [177Lu]lutetium sesquioxide-iFAP/iPSMA nanoparticles ([177Lu]Lu−iFAP/iPSMA) inhibit HCT116 tumor progression in mice. Understanding the toxicity of [177Lu]Lu−iFAP/iPSMA in healthy tissues, as well as at the tissue and cellular level in pathological settings, is essential to demonstrate the nanosystem safety for treating patients. It is equally important to demonstrate that [177Lu]Lu−iFAP/iPSMA can be prepared under good manufacturing practices (GMP) with reproducible pharmaceutical-grade quality characteristics. This research aimed to prepare [177Lu]Lu−iFAP/iPSMA under GMP-compliant radiopharmaceutical processes and evaluate its toxicity in cell cultures and murine biological systems under pathological environments. [177Lu]Lu2O3 nanoparticles were formulated as radiocolloidal solutions with FAP and PSMA inhibitor ligands (iFAP and iPSMA), sodium citrate, and gelatin, followed by heating at 121 °C (103-kPa pressure) for 15 min. Three consecutive batches were manufactured. The final product was analyzed according to conventional pharmacopeial methods. The Lu content in the formulations was determined by X-ray fluorescence. [177Lu]Lu−iFAP/iPSMA performance in cancer cells was evaluated in vitro by immunofluorescence. Histopathological toxicity in healthy and tumor tissues was assessed in HCT116 tumor-bearing mice. Immunohistochemical assays were performed to corroborate FAP and PSMA tumor expression. Acute genotoxicity was evaluated using the micronuclei assay. The results showed that the batches manufactured under GMP conditions were reproducible. Radiocolloidal solutions were sterile and free of bacterial endotoxins, with radionuclidic and radiochemical purity greater than 99%. The lutetium content was 0.10 ± 0.02 mg/mL (0.9 GBq/mg). Significant inhibition of cell proliferation in vitro and in tumors was observed due to the accumulation of nanoparticles in the fibroblasts (FAP+) and neovasculature (PSMA+) of the tumor microenvironment. No histopathological damage was detected in healthy tissues. The data obtained in this research provide new evidence on the selective toxicity to malignant tumors and the absence of histological changes in healthy tissues after intravenous injection of [177Lu]Lu−iFAP/iPSMA in mammalian hosts. The easy preparation under GMP conditions and the toxicity features provide the added value needed for [177Lu]Lu−iFAP/iPSMA clinical translation. Full article
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15 pages, 4350 KiB  
Article
Ag-Activated Metal−Organic Framework with Peroxidase-like Activity Synergistic Ag+ Release for Safe Bacterial Eradication and Wound Healing
by Jie Zhou, Ning Chen, Jing Liao, Gan Tian, Linqiang Mei, Guoping Yang, Qiang Wang and Wenyan Yin
Nanomaterials 2022, 12(22), 4058; https://doi.org/10.3390/nano12224058 - 17 Nov 2022
Cited by 9 | Viewed by 2317
Abstract
Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag+ [...] Read more.
Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag+ in the bacterial microenvironment. Here, we report a porous metal−organic framework (MOF)-based Zr-2-amin-1,4-NH2-benzenedicarboxylate@Ag (denoted as UiO-66-NH2-Ag) nanocomposite using an in-situ immobilization strategy where Ag NPs were fixed on the UiO-66-NH2 for improving the dispersion and utilization of Ag NPs. As a result, the reduced use dose of Ag NPs largely improves the biosafety of the UiO-66-NH2-Ag. Meanwhile, after activation by the Ag NPs, the UiO-66-NH2-Ag can act as nanozyme with high peroxidase (POD)-like activity to efficiently catalyze the decomposition of H2O2 to extremely toxic hydroxyl radicals (·OH) in the bacterial microenvironment. Simultaneously, the high POD-like activity synergies with the controllable Ag+ release leads to enhanced reactive oxygen species (ROS) generation, facilitating the death of resistant bacteria. This synergistic antibacterial strategy enables the low concentration (12 μg/mL) of UiO-66-NH2-Ag to achieve highly efficient inactivation of ampicillin-resistant Escherichia coli (AmprE. coli) and endospore-forming Bacillus subtilis (B. subtilis). In vivo results illustrate that the UiO-66-NH2-Ag nanozyme has a safe and accelerated bacteria-infected wound healing. Full article
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17 pages, 3825 KiB  
Article
Different Strategies to Attenuate the Toxic Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells
by Mariana Vassal, Cátia D. Pereira, Filipa Martins, Vera L. M. Silva, Artur M. S. Silva, Ana M. R. Senos, Maria Elisabete V. Costa, Maria de Lourdes Pereira and Sandra Rebelo
Nanomaterials 2022, 12(20), 3561; https://doi.org/10.3390/nano12203561 - 11 Oct 2022
Cited by 1 | Viewed by 1860
Abstract
Zinc oxide nanoparticles (ZnO NPs) are one of the most used nanoparticles due to their unique physicochemical and biological properties. There is, however, a growing concern about their negative impact on male reproductive health. Therefore, in the present study, two different strategies were [...] Read more.
Zinc oxide nanoparticles (ZnO NPs) are one of the most used nanoparticles due to their unique physicochemical and biological properties. There is, however, a growing concern about their negative impact on male reproductive health. Therefore, in the present study, two different strategies were used to evaluate the recovery ability of spermatogonia cells from the first stage of spermatogenesis (GC-1 spg cell line) after being exposed to a cytotoxic concentration of ZnO NPs (20 µg/mL) for two different short time periods, 6 and 12 h. The first strategy was to let the GC-1 cells recover after ZnO NPs exposure in a ZnO NPs-free medium for 4 days. At this phase, cell viability assays were performed to evaluate whether this period was long enough to allow for cell recovery. Exposure to ZnO NPs for 6 h and 12 h induced a decrease in viability of 25% and 41%, respectively. However, the recovery period allowed for an increase in cell viability from 16% to 25% to values as high as 91% and 84%. These results strongly suggest that GC-1 cells recover, but not completely, given that the cell viability does not reach 100%. Additionally, the impact of a synthetic chalcone (E)-3-(2,6-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) to counteract the reproductive toxicity of ZnO NPs was investigated. Different concentrations of chalcone 1 (0–12.5 µM) were used before and during exposure of GC-1 cells to ZnO NPs to mitigate the damage induced by NPs. The protective ability of this compound was evaluated through viability assays, levels of DNA damage, and cytoskeleton dynamics (evaluating the acetylated α-tubulin and β-actin protein levels). The results indicated that the tested concentrations of chalcone 1 can attenuate the genotoxicity induced by ZnO NPs for shorter exposure periods (6 h). Chalcone 1 supplementation also increased cell viability and stabilized the microtubules. However, the antioxidant potential of this compound remains to be elucidated. In conclusion, this work addressed the main cytotoxic effects of ZnO NPs on a spermatogonia cell line and analyzed two different strategies to mitigate this damage, which represent a significant contribution to the field of male fertility. Full article
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18 pages, 3340 KiB  
Article
Could Iron-Nitrogen Doping Modulate the Cytotoxicity of TiO2 Nanoparticles?
by Ionela Cristina Nica, Bogdan Andrei Miu, Miruna S. Stan, Lucian Diamandescu and Anca Dinischiotu
Nanomaterials 2022, 12(5), 770; https://doi.org/10.3390/nano12050770 - 25 Feb 2022
Cited by 2 | Viewed by 1958
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) are found in several products on the market that include paints, smart textiles, cosmetics and food products. Besides these, TiO2 NPs are intensively researched for their use in biomedicine, agriculture or installations to produce energy. Taking [...] Read more.
Titanium dioxide nanoparticles (TiO2 NPs) are found in several products on the market that include paints, smart textiles, cosmetics and food products. Besides these, TiO2 NPs are intensively researched for their use in biomedicine, agriculture or installations to produce energy. Taking into account that several risks have been associated with the use of TiO2 NPs, our aim was to provide TiO2 NPs with improved qualities and lower toxicity to humans and the environment. Pure TiO2 P25 NPs and the same NPs co-doped with iron (1%) and nitrogen atoms (P25-Fe(1%)-N NPs) by hydrothermal treatment to increase the photocatalytic activity in the visible light spectrum were in vitro evaluated in the presence of human lung cells. After 24 and 72 h of incubation, the oxidative stress was initiated in a time- and dose-dependent manner with major differences between pure P25 and P25-Fe(1%)-N NPs as revealed by malondialdehyde and reactive oxygen species levels. Additionally, a lower dynamic of autophagic vacuoles formation was observed in cells exposed to Fe-N-doped P25 NPs compared to the pure ones. Therefore, our results suggest that Fe-N doping of TiO2 NPs can represent a valuable alternative to the conventional P25 Degussa particles in industrial and medical applications. Full article
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Review

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23 pages, 2522 KiB  
Review
Nanoparticle Impact on the Bacterial Adaptation: Focus on Nano-Titania
by Maria Grazia Ammendolia and Barbara De Berardis
Nanomaterials 2022, 12(20), 3616; https://doi.org/10.3390/nano12203616 - 15 Oct 2022
Cited by 20 | Viewed by 2209
Abstract
Titanium dioxide nanoparticles (nano-titania/TiO2 NPs) are used in different fields and applications. However, the release of TiO2 NPs into the environment has raised concerns about their biosafety and biosecurity. In light of the evidence that TiO2 NPs could be used [...] Read more.
Titanium dioxide nanoparticles (nano-titania/TiO2 NPs) are used in different fields and applications. However, the release of TiO2 NPs into the environment has raised concerns about their biosafety and biosecurity. In light of the evidence that TiO2 NPs could be used to counteract antibiotic resistance, they have been investigated for their antibacterial activity. Studies reported so far indicate a good performance of TiO2 NPs against bacteria, alone or in combination with antibiotics. However, bacteria are able to invoke multiple response mechanisms in an attempt to adapt to TiO2 NPs. Bacterial adaption arises from global changes in metabolic pathways via the modulation of regulatory networks and can be related to single-cell or multicellular communities. This review describes how the impact of TiO2 NPs on bacteria leads to several changes in microorganisms, mainly during long-term exposure, that can evolve towards adaptation and/or increased virulence. Strategies employed by bacteria to cope with TiO2 NPs suggest that their use as an antibacterial agent has still to be extensively investigated from the point of view of the risk of adaptation, to prevent the development of resistance. At the same time, possible effects on increased virulence following bacterial target modifications by TiO2 NPs on cells or tissues have to be considered. Full article
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34 pages, 1113 KiB  
Review
A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles: Evidence from Transcriptomics Studies
by Shuyuan Wang, Harri Alenius, Hani El-Nezami and Piia Karisola
Nanomaterials 2022, 12(8), 1247; https://doi.org/10.3390/nano12081247 - 7 Apr 2022
Cited by 19 | Viewed by 3761
Abstract
Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) have attracted a great deal of attention due to their excellent electrical, optical, whitening, UV-adsorbing and bactericidal properties. The extensive production and utilization of these NPs increases their chances of being released [...] Read more.
Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) have attracted a great deal of attention due to their excellent electrical, optical, whitening, UV-adsorbing and bactericidal properties. The extensive production and utilization of these NPs increases their chances of being released into the environment and conferring unintended biological effects upon exposure. With the increasingly prevalent use of the omics technique, new data are burgeoning which provide a global view on the overall changes induced by exposures to NPs. In this review, we provide an account of the biological effects of ZnO and TiO2 NPs arising from transcriptomics in in vivo and in vitro studies. In addition to studies on humans and mice, we also describe findings on ecotoxicology-related species, such as Danio rerio (zebrafish), Caenorhabditis elegans (nematode) or Arabidopsis thaliana (thale cress). Based on evidence from transcriptomics studies, we discuss particle-induced biological effects, including cytotoxicity, developmental alterations and immune responses, that are dependent on both material-intrinsic and acquired/transformed properties. This review seeks to provide a holistic insight into the global changes induced by ZnO and TiO2 NPs pertinent to human and ecotoxicology. Full article
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