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Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles

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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 11922

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Special Issue Editor

Prof. Dr. Wenyan Yin

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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, MoO_x, Fe₂O₃, and CuO_x, 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

Manuscript Submission Information

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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

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

Published Papers (6 papers)

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Research

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19 pages, 6802 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/nano12234181 - 25 Nov 2022

Cited by 8 | Viewed by 1505

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 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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15 pages, 4350 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/nano12224058 - 17 Nov 2022

Cited by 6 | Viewed by 1771

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⁺ 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 (Amp^rE. 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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17 pages, 3825 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/nano12203561 - 11 Oct 2022

Viewed by 1521

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 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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18 pages, 3340 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/nano12050770 - 25 Feb 2022

Cited by 1 | Viewed by 1588

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 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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Review

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23 pages, 2522 KiB

Open AccessReview

Nanoparticle Impact on the Bacterial Adaptation: Focus on Nano-Titania

by Maria Grazia Ammendolia and Barbara De Berardis

Nanomaterials 2022, 12(20), 3616; https://0-doi-org.brum.beds.ac.uk/10.3390/nano12203616 - 15 Oct 2022

Cited by 8 | Viewed by 1551

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 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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34 pages, 1113 KiB

Open AccessEditor’s ChoiceReview

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://0-doi-org.brum.beds.ac.uk/10.3390/nano12081247 - 07 Apr 2022

Cited by 13 | Viewed by 2998

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 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

(This article belongs to the Special Issue Toxicity Assessment of Metal Nanoparticles and Metal Oxide Nanoparticles)

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