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Nanomaterials
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Advances in Nanotoxicology
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Advances in Nanotoxicology

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 70338

Special Issue Editors

Dr. Anne Kahru

E-Mail Website
Guest Editor
National Institute of Chemical Physics and Biophysics (NICPB), Laboratory of Environmental Toxicology, Akadeemia Tee 23, 12618 Tallinn, Estonia
Interests: nanotoxicology; ecotoxicology; microbiology; in vitro toxicology; antimicrobials; 3Rs
Special Issues, Collections and Topics in MDPI journals
Dr. Monika Mortimer

E-Mail Website
Guest Editor
Institute of Environmental and Health Sciences, College of Quality and Safety Engineering, China Jiliang University, Hangzhou, China
Interests: ecotoxicology; nanotoxicology; engineered nanomaterials; microbiology; mechanisms of toxicity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With increased requirement for novel materials to facilitate societal progress, nanomaterials have been at the forefront of industry and various applications for more than several decades. Another side of the coin is the safety of these nano-enabled products. Safety is of prime importance to the sustainability of any novel technological approach, including nanotechnology. Thus, the main areas of focus of nanotoxicology include: (i) safety assessment of novel nanomaterials; (ii) elucidating toxicity mechanisms of nanomaterials to enable safe-by-design product development, and (iii) discovery of novel biological properties of nanomaterials for applications such as water treatment, nanomedicines, and nanoagrochemicals. This Special Issue aims to provide an overview of the recent developments in nanotoxicology research, including but not limited to:

  • experimental and theoretical approaches such as high-throughput assays, omics methods, novel in vitro models, cell co-cultures, systems biology, and nanoinformatics approaches;
  • assessment of nanomaterial effects on novel endpoints such as microbiome, inter- and intracellular, -organismal or -species interactions, and plant, animal or human diseases;
  • elucidation of toxicity mechanisms of nanomaterials;
  • nanoecotoxicity testing in environmentally relevant conditions and at environmentally relevant nanomaterial concentrations and physicochemical states;
  • safety evaluation of novel nanomaterial applications in water treatment, agriculture, medicine, environmental remediation and other fields;
  • developments in computational toxicology of nanomaterials, including predictive modeling, development of read-across and QSAR models, models related to adverse outcome pathways (AOP), and others.

Prof. Dr. Anne Kahru
Assoc. Prof. Dr. Monika Mortimer
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

  • Nanotoxicology
  • Nanoecotoxicology
  • Nanosafety
  • Safety of nanomedicines
  • Safety of nanoagrochemicals
  • Biocompatibility
  • Nanoantimicrobials
  • Hazard and exposure assessment
  • Mechanisms of action
  • Computational toxicology

Published Papers (16 papers)

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Editorial

Jump to: Research, Review

4 pages, 190 KiB  
Editorial
Advances in Nanotoxicology: Towards Enhanced Environmental and Physiological Relevance and Molecular Mechanisms
by Anne Kahru and Monika Mortimer
Nanomaterials 2021, 11(4), 919; https://doi.org/10.3390/nano11040919 - 4 Apr 2021
Cited by 2 | Viewed by 1769
Abstract
Nanotoxicology, a discipline transpired by the need to assess the human and environmental safety of nanoscale materials, has evolved over the past 15 years into a mature area of toxicology [...] Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)

Research

Jump to: Editorial, Review

11 pages, 2245 KiB  
Article
Combined Toxicity of TiO2 Nanospherical Particles and TiO2 Nanotubes to Two Microalgae with Different Morphology
by Zhuang Wang, Shiguang Jin, Fan Zhang and Degao Wang
Nanomaterials 2020, 10(12), 2559; https://doi.org/10.3390/nano10122559 - 20 Dec 2020
Cited by 9 | Viewed by 2586
Abstract
The joint activity of multiple engineered nanoparticles (ENPs) has attracted much attention in recent years. Many previous studies have focused on the combined toxicity of different ENPs with nanostructures of the same dimension. However, the mixture toxicity of multiple ENPs with different dimensions [...] Read more.
The joint activity of multiple engineered nanoparticles (ENPs) has attracted much attention in recent years. Many previous studies have focused on the combined toxicity of different ENPs with nanostructures of the same dimension. However, the mixture toxicity of multiple ENPs with different dimensions is much less understood. Herein, we investigated the toxicity of the binary mixture of TiO2 nanospherical particles (NPs) and TiO2 nanotubes (NTs) to two freshwater algae with different morphology, namely, Scenedesmus obliquus and Chlorella pyrenoidosa. The physicochemical properties, dispersion stability, and the generation of reactive oxygen species (ROS) were determined in the single and binary systems. Classical approaches to assessing mixture toxicity were applied to evaluate and predict the toxicity of the binary mixtures. The results show that the combined toxicity of TiO2 NPs and NTs to S. obliquus was between the single toxicity of TiO2 NTs and NPs, while the combined toxicity to C. pyrenoidosa was higher than their single toxicity. Moreover, the toxicity of the binary mixtures to C. pyrenoidosa was higher than that to S. obliquus. A toxic unit assessment showed that the effects of TiO2 NPs and NTs were additive to the algae. The combined toxicity to S. obliquus and C. pyrenoidosa can be effectively predicted by the concentration addition model and the independent action model, respectively. The mechanism of the toxicity caused by the binary mixtures of TiO2 NPs and NTs may be associated with the dispersion stability of the nanoparticles in aquatic media and the ROS-induced oxidative stress effects. Our results may offer a new insight into evaluating and predicting the combined toxicological effects of ENPs with different dimensions and of probing the mechanisms involved in their joint toxicity. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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15 pages, 1813 KiB  
Article
Long-Term Toxicity of ZnO Nanoparticles on Scenedesmus rubescens Cultivated in Semi-Batch Mode
by Andriana F. Aravantinou, Fytoula Andreou and Ioannis D. Manariotis
Nanomaterials 2020, 10(11), 2262; https://doi.org/10.3390/nano10112262 - 16 Nov 2020
Cited by 10 | Viewed by 2054
Abstract
The scope of this study was to investigate the toxic effects of zinc oxide (ZnO) nanoparticles (NPs) on freshwater microalgae, in long-term semi-batch feeding mode at two different hydraulic retention times (HRTs) (20 and 40 days). A freshwater microalgae, Scenedesmus rubescens, was employed [...] Read more.
The scope of this study was to investigate the toxic effects of zinc oxide (ZnO) nanoparticles (NPs) on freshwater microalgae, in long-term semi-batch feeding mode at two different hydraulic retention times (HRTs) (20 and 40 days). A freshwater microalgae, Scenedesmus rubescens, was employed and exposed to a semi-continuous supply of ZnO NPs at a low concentration of 0.081 mg/L for a period of 28 d. Experiments were conducted under controlled environmental conditions. Τhe impact of ZnO NPs on S. rubescens, which was assessed in terms of nutrient removal, biomass growth, and algal lipid content. Semi-batch mode cultures showed that low ZnO NP concentrations at an HRT of 40 d did not have any negative effect on microalgae growth after the fourth day of culture. In contrast, algal growth was inhibited up to 17.5% at an HRT of 20 d in the presence of ZnO NPs. This might be attributed to the higher flow rate applied and ZnO NPs load. A positive correlation between nutrient removal and microalgae growth was observed. The algal lipid content was, in most cases, higher in the presence of ZnO NPs at both HRTs, indicating that even low ZnO NPs concentration cause stress resulting in higher lipid content. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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15 pages, 8533 KiB  
Article
In Vitro Study of the Toxicity Mechanisms of Nanoscale Zero-Valent Iron (nZVI) and Released Iron Ions Using Earthworm Cells
by Jaroslav Semerad, Natividad Isabel Navarro Pacheco, Alena Grasserova, Petra Prochazkova, Martin Pivokonsky, Lenka Pivokonska and Tomas Cajthaml
Nanomaterials 2020, 10(11), 2189; https://doi.org/10.3390/nano10112189 - 3 Nov 2020
Cited by 15 | Viewed by 2680
Abstract
During the last two decades, nanomaterials based on nanoscale zero-valent iron (nZVI) have ranked among the most utilized remediation technologies for soil and groundwater cleanup. The high reduction capacity of elemental iron (Fe0) allows for the rapid and cost-efficient degradation or [...] Read more.
During the last two decades, nanomaterials based on nanoscale zero-valent iron (nZVI) have ranked among the most utilized remediation technologies for soil and groundwater cleanup. The high reduction capacity of elemental iron (Fe0) allows for the rapid and cost-efficient degradation or transformation of many organic and inorganic pollutants. Although worldwide real and pilot applications show promising results, the effects of nZVI on exposed living organisms are still not well explored. The majority of the recent studies examined toxicity to microbes and to a lesser extent to other organisms that could also be exposed to nZVI via nanoremediation applications. In this work, a novel approach using amoebocytes, the immune effector cells of the earthworm Eisenia andrei, was applied to study the toxicity mechanisms of nZVI. The toxicity of the dissolved iron released during exposure was studied to evaluate the effect of nZVI aging with regard to toxicity and to assess the true environmental risks. The impact of nZVI and associated iron ions was studied in vitro on the subcellular level using different toxicological approaches, such as short-term immunological responses and oxidative stress. The results revealed an increase in reactive oxygen species production following nZVI exposure, as well as a dose-dependent increase in lipid peroxidation. Programmed cell death (apoptosis) and necrosis were detected upon exposure to ferric and ferrous ions, although no lethal effects were observed at environmentally relevant nZVI concentrations. The decreased phagocytic activity further confirmed sublethal adverse effects, even after short-term exposure to ferric and ferrous iron. Detection of sublethal effects, including changes in oxidative stress-related markers such as reactive oxygen species and malondialdehyde production revealed that nZVI had minimal impacts on exposed earthworm cells. In comparison to other works, this study provides more details regarding the effects of the individual iron forms associated with nZVI aging and the cell toxicity effects on the specific earthworms’ immune cells that represent a suitable model for nanomaterial testing. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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15 pages, 3498 KiB  
Article
Titanium Dioxide Nanoparticles Induced HeLa Cell Necrosis under UVA Radiation through the ROS-mPTP Pathway
by Runqing Geng, Yuanyuan Ren, Rong Rao, Xi Tan, Hong Zhou, Xiangliang Yang, Wei Liu and Qunwei Lu
Nanomaterials 2020, 10(10), 2029; https://doi.org/10.3390/nano10102029 - 15 Oct 2020
Cited by 12 | Viewed by 3125
Abstract
Titanium dioxide nanoparticles (nano-TiO2), as a common nanomaterial, are widely used in water purification, paint, skincare and sunscreens. Its safety has always been a concern. Prior studies have shown that ultraviolet A (UVA) can exacerbate the toxicity of nano-TiO2, [...] Read more.
Titanium dioxide nanoparticles (nano-TiO2), as a common nanomaterial, are widely used in water purification, paint, skincare and sunscreens. Its safety has always been a concern. Prior studies have shown that ultraviolet A (UVA) can exacerbate the toxicity of nano-TiO2, including inducing cell apoptosis, changing glycosylation levels, arresting cell cycle, inhibiting tumor cell and bacterial growth. However, whether the combination of UVA and nano-TiO2 cause cell necrosis and its mechanism are still rarely reported. In this study, we investigated the cytotoxicity and phototoxicity of mixture crystalline nano-TiO2 (25% rutile and 75% anatase, 21 nm) under UVA irradiation in HeLa cells. Our results showed that the abnormal membrane integrity and the ultrastructure of HeLa cells, together with the decreased viability induced by nano-TiO2 under UVA irradiation, were due to cell necrosis rather than caspase-dependent apoptosis. Furthermore, nano-TiO2 and UVA generated the reactive oxygen species (ROS) and caused the mitochondrial permeability transition pore (mPTP) of HeLa cells to abnormally open. Cell viability was significantly increased after adding vitamin C (VC) or cyclosporin A (CsA) individually to inhibit ROS and mPTP. Clearance of ROS could not only impede the opening of mPTP but also reduce the rate of cell necrosis. The results suggest the possible mechanism of HeLa cell necrosis caused by nano-TiO2 under UVA irradiation through the ROS-mPTP pathway. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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18 pages, 2819 KiB  
Article
Effects of Humic Acids on the Ecotoxicity of Fe3O4 Nanoparticles and Fe-Ions: Impact of Oxidation and Aging
by Lyubov Bondarenko, Anne Kahru, Vera Terekhova, Gulzhian Dzhardimalieva, Pavel Uchanov and Kamila Kydralieva
Nanomaterials 2020, 10(10), 2011; https://doi.org/10.3390/nano10102011 - 12 Oct 2020
Cited by 15 | Viewed by 2442
Abstract
The magnetite nanoparticles (MNPs) are increasingly produced and studied for various environmental applications, yet the information on their ecotoxicity is scarce. We evaluated the ecotoxicity of MNPs (~7 nm) before and after the addition of humic acids (HAs). White mustard Sinapis alba and [...] Read more.
The magnetite nanoparticles (MNPs) are increasingly produced and studied for various environmental applications, yet the information on their ecotoxicity is scarce. We evaluated the ecotoxicity of MNPs (~7 nm) before and after the addition of humic acids (HAs). White mustard Sinapis alba and unicellular ciliates Paramecium caudatum were used as test species. The MNPs were modified by HAs and oxidized/aged under mild and harsh conditions. Bare MNPs proved not toxic to plants (96 h EC50 > 3300 mg/L) but the addition of HAs and mild oxidation increased their inhibitory effect, especially after harsh oxidation (96 h EC50 = 330 mg/L). Nevertheless, all these formulations could be ranked as ‘not harmful’ to S. alba (i.e., 96 h EC50 > 100 mg/L). The same tendency was observed for ciliates, but the respective EC50 values ranged from ‘harmful’ (24 h EC50 = 10–100 mg/L) to ‘very toxic’ (24 h EC50 < 1 mg/L). The ecotoxicity of Fe-ions with and without the addition of HAs was evaluated in parallel: Fe (II) and Fe (III) ions were toxic to S. alba (96 h EC50 = 35 and 60 mg/L, respectively) and even more toxic to ciliates (24 h EC50 = 1 and 3 mg/L, respectively). Addition of the HAs to Fe-ions yielded the respective complexes not harmful to plants (96h EC50 > 100 mg/L) but toxic to ciliates (24 h EC50 = 10–100 mg/L). These findings will be helpful for the understanding of the environmental fate and toxicity of iron-based NPs. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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21 pages, 4180 KiB  
Article
Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation
by Khanh Nguyen, Bianca Nuß, Marina Mühlberger, Harald Unterweger, Ralf P. Friedrich, Christoph Alexiou and Christina Janko
Nanomaterials 2020, 10(8), 1577; https://doi.org/10.3390/nano10081577 - 11 Aug 2020
Cited by 13 | Viewed by 3324
Abstract
Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired [...] Read more.
Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired as well. This limits the administered dose and eventually allows tumor cells to escape treatment. In order to increase intratumoral drug concentration and simultaneously reduce systemic side effects, nanoparticles have come into focus as drug carriers. The functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with chemotherapeutics such as mitoxantrone (MTO) enables targeted drug transport by using magnetic forces. Here, we investigate SPIONs consisting of individual iron oxide cores of 10 nm in diameter and a total hydrodynamic diameter of 53 ± 0.8 nm as a transporting system for MTO. Comparing the killing efficacy in monolayer cell culture and multicellular tumor spheroids of HT-29 cells, we show that spheroids tolerate considerably higher doses of nanoparticle-loaded MTO. Therefore, dose predictions from conventional monolayer cell cultures are often misleading for in vivo applications. This was true for both soluble and nanoparticle-bound MTO. Using flow chambers mimicking in vivo blood flow, we furthermore demonstrate that SPIONs can magnetically accumulate MTO. We conclude that SPIONs can function as an effective delivery platform to increase local drug concentrations, thereby potentially overcoming chemotherapy resistance of cells. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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18 pages, 2356 KiB  
Article
Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials
by Taisuke Tomonaga, Hiroto Izumi, Takako Oyabu, Byeong-Woo Lee, Masaru Kubo, Manabu Shimada, Shingo Noguchi, Chinatsu Nishida, Kazuhiro Yatera and Yasuo Morimoto
Nanomaterials 2020, 10(8), 1563; https://doi.org/10.3390/nano10081563 - 9 Aug 2020
Cited by 11 | Viewed by 2704
Abstract
This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of [...] Read more.
This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after intratracheal instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following intratracheal instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both intratracheal instillation and inhalation exposure. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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20 pages, 3922 KiB  
Article
Effects of Modified Magnetite Nanoparticles on Bacterial Cells and Enzyme Reactions
by Lyubov S. Bondarenko, Ekaterina S. Kovel, Kamila A. Kydralieva, Gulzhian I. Dzhardimalieva, Erzsébet Illés, Etelka Tombácz, Arina G. Kicheeva and Nadezhda S. Kudryasheva
Nanomaterials 2020, 10(8), 1499; https://doi.org/10.3390/nano10081499 - 30 Jul 2020
Cited by 29 | Viewed by 3810
Abstract
Current paper presents biological effects of magnetite nanoparticles (MNPs). Relations of MNP’ characteristics (zeta-potential and hydrodynamic diameters) with effects on bacteria and their enzymatic reactions were the main focus. Photobacterium phosphoreum and bacterial enzymatic reactions were chosen as bioassays. Three types of MNPs [...] Read more.
Current paper presents biological effects of magnetite nanoparticles (MNPs). Relations of MNP’ characteristics (zeta-potential and hydrodynamic diameters) with effects on bacteria and their enzymatic reactions were the main focus. Photobacterium phosphoreum and bacterial enzymatic reactions were chosen as bioassays. Three types of MNPs were under study: bare Fe3O4, Fe3O4 modified with 3-aminopropyltriethoxysilane (Fe3O4/APTES), and humic acids (Fe3O4/HA). Effects of the MNPs were studied at a low concentration range (< 2 mg/L) and attributed to availability and oxidative activity of Fe3+, high negative surface charge, and low hydrodynamic diameter of Fe3O4/HA, as well as higher Fe3+ content in suspensions of Fe3O4/HA. Low-concentration suspensions of bare Fe3O4 provided inhibitory effects in both bacterial and enzymatic bioassays, whereas the MNPs with modified surface (Fe3O4/APTES and Fe3O4/HA) did not affect the enzymatic activity. Under oxidative stress (i.e., in the solutions of model oxidizer, 1,4-benzoquinone), MNPs did not reveal antioxidant activity, moreover, Fe3O4/HA demonstrated additional inhibitory activity. The study contributes to the deeper understanding of a role of humic substances and silica in biogeochemical cycling of iron. Bioluminescence assays, cellular and enzymatic, can serve as convenient tools to evaluate bioavailability of Fe3+ in natural dispersions of iron-containing nanoparticles, e.g., magnetite, ferrihydrite, etc. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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19 pages, 3286 KiB  
Article
Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid
by Maddalena Sguizzato, Paolo Mariani, Francesca Ferrara, Markus Drechsler, Supandeep Singh Hallan, Nicolas Huang, Fanny Simelière, Nikul Khunti, Rita Cortesi, Nicola Marchetti, Giuseppe Valacchi and Elisabetta Esposito
Nanomaterials 2020, 10(5), 961; https://doi.org/10.3390/nano10050961 - 18 May 2020
Cited by 23 | Viewed by 3391
Abstract
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been [...] Read more.
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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23 pages, 6574 KiB  
Article
A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats
by Maria Enea, Ana Margarida Araújo, Miguel Peixoto de Almeida, Maria Elisa Soares, Salomé Gonçalves-Monteiro, Paula Guedes de Pinho, Eulália Pereira, Maria de Lourdes Bastos and Helena Carmo
Nanomaterials 2019, 9(11), 1606; https://doi.org/10.3390/nano9111606 - 12 Nov 2019
Cited by 16 | Viewed by 3010
Abstract
Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and [...] Read more.
Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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Review

Jump to: Editorial, Research

36 pages, 5324 KiB  
Review
Nanotheranostics: A Possible Solution for Drug-Resistant Staphylococcus aureus and their Biofilms?
by Dina A. Mosselhy, Mhd Assad, Tarja Sironen and Mady Elbahri
Nanomaterials 2021, 11(1), 82; https://doi.org/10.3390/nano11010082 - 2 Jan 2021
Cited by 24 | Viewed by 5071
Abstract
Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. [...] Read more.
Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. Treating biofilms is problematic except via implant removal or wound debridement. Nanoparticles (NPs) and nanofibers could combat superbugs and biofilms and rapidly diagnose MRSA. Nanotheranostics combine diagnostics and therapeutics into a single agent. This comprehensive review is interpretative, utilizing mainly recent literature (since 2016) besides the older remarkable studies sourced via Google Scholar and PubMed. We unravel the molecular S. aureus resistance and complex biofilm. The diagnostic properties and detailed antibacterial and antibiofilm NP mechanisms are elucidated in exciting stories. We highlight the challenges of bacterial infections nanotheranostics. Finally, we discuss the literature and provide “three action appraisals”. (i) The first appraisal consists of preventive actions (two wings), avoiding unnecessary hospital visits, hand hygiene, and legislations against over-the-counter antibiotics as the general preventive wing. Our second recommended preventive wing includes preventing the adverse side effects of the NPs from resistance and toxicity by establishing standard testing procedures. These standard procedures should provide breakpoints of bacteria’s susceptibility to NPs and a thorough toxicological examination of every single batch of synthesized NPs. (ii) The second appraisal includes theranostic actions, using nanotheranostics to diagnose and treat MRSA, such as what we call “multifunctional theranostic nanofibers. (iii) The third action appraisal consists of collaborative actions. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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18 pages, 2089 KiB  
Review
Application of Nanoparticles Alleviates Heavy Metals Stress and Promotes Plant Growth: An Overview
by Pingfan Zhou, Muhammad Adeel, Noman Shakoor, Manlin Guo, Yi Hao, Imran Azeem, Mingshu Li, Mengyuan Liu and Yukui Rui
Nanomaterials 2021, 11(1), 26; https://doi.org/10.3390/nano11010026 - 24 Dec 2020
Cited by 134 | Viewed by 7696
Abstract
Nanotechnology is playing a significant role in addressing a vast range of environmental challenges by providing innovative and effective solutions. Heavy metal (HM) contamination has gained considerable attention in recent years due their rapidly increasing concentrations in agricultural soil. Due to their unique [...] Read more.
Nanotechnology is playing a significant role in addressing a vast range of environmental challenges by providing innovative and effective solutions. Heavy metal (HM) contamination has gained considerable attention in recent years due their rapidly increasing concentrations in agricultural soil. Due to their unique physiochemical properties, nanoparticles (NPs) can be effectively applied for stress alleviation. In this review, we explore the current status of the literature regarding nano-enabled agriculture retrieved from the Web of Science databases and published from January 2010 to November 2020, with most of our sources spanning the past five years. We briefly discuss uptake and transport mechanisms, application methods (soil, hydroponic and foliar), exposure concentrations, and their impact on plant growth and development. The current literature contained sufficient information about NPs behavior in plants in the presence of pollutants, highlighting the alleviation mechanism to overcome the HM stress. Furthermore, we present a broad overview of recent advances regarding HM stress and the possible mechanism of interaction between NPs and HM in the agricultural system. Additionally, this review article will be supportive for the understanding of phytoremediation and micro-remediation of contaminated soils and also highlights the future research needs for the combined application of NPs in the soil for sustainable agriculture. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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41 pages, 3648 KiB  
Review
Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine
by Jossana A. Damasco, Saisree Ravi, Joy D. Perez, Daniel E. Hagaman and Marites P. Melancon
Nanomaterials 2020, 10(11), 2186; https://doi.org/10.3390/nano10112186 - 2 Nov 2020
Cited by 46 | Viewed by 9383
Abstract
Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique [...] Read more.
Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to their translation. Successful clinical translation of these nanoparticles is heavily dependent on their stability, circulation time, access and bioavailability to disease sites, and their safety profile. This review covers preclinical and clinical inorganic-nanoparticle based nanomaterial utilized for cancer imaging and therapeutics. A special emphasis is put on the rational design to develop non-toxic/safe inorganic nanoparticle constructs to increase their viability as translatable nanomedicine for cancer therapies. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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35 pages, 2143 KiB  
Review
In Vitro and In Vivo Models for Evaluating the Oral Toxicity of Nanomedicines
by Sudeep Lama, Olivier Merlin-Zhang and Chunhua Yang
Nanomaterials 2020, 10(11), 2177; https://doi.org/10.3390/nano10112177 - 31 Oct 2020
Cited by 18 | Viewed by 4592
Abstract
Toxicity studies for conventional oral drug formulations are standardized and well documented, as required by the guidelines of administrative agencies such as the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or European Medicines Evaluation Agency (EMEA), and the Japanese [...] Read more.
Toxicity studies for conventional oral drug formulations are standardized and well documented, as required by the guidelines of administrative agencies such as the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or European Medicines Evaluation Agency (EMEA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Researchers tend to extrapolate these standardized protocols to evaluate nanoformulations (NFs) because standard nanotoxicity protocols are still lacking in nonclinical studies for testing orally delivered NFs. However, such strategies have generated many inconsistent results because they do not account for the specific physicochemical properties of nanomedicines. Due to their tiny size, accumulated surface charge and tension, sizeable surface-area-to-volume ratio, and high chemical/structural complexity, orally delivered NFs may generate severe topical toxicities to the gastrointestinal tract and metabolic organs, including the liver and kidney. Such toxicities involve immune responses that reflect different mechanisms than those triggered by conventional formulations. Herein, we briefly analyze the potential oral toxicity mechanisms of NFs and describe recently reported in vitro and in vivo models that attempt to address the specific oral toxicity of nanomedicines. We also discuss approaches that may be used to develop nontoxic NFs for oral drug delivery. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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28 pages, 812 KiB  
Review
Review of Copper and Copper Nanoparticle Toxicity in Fish
by Nemi Malhotra, Tzong-Rong Ger, Boontida Uapipatanakul, Jong-Chin Huang, Kelvin H.-C. Chen and Chung-Der Hsiao
Nanomaterials 2020, 10(6), 1126; https://doi.org/10.3390/nano10061126 - 7 Jun 2020
Cited by 140 | Viewed by 11335
Abstract
This review summarizes the present knowledge on the toxicity of copper and copper nanoparticles (CuNPs) to various fish species. In previous decades, the excessive usage of metal and metallic nanoparticles has increased significantly, increasing the probability of the accumulation and discharge of metals [...] Read more.
This review summarizes the present knowledge on the toxicity of copper and copper nanoparticles (CuNPs) to various fish species. In previous decades, the excessive usage of metal and metallic nanoparticles has increased significantly, increasing the probability of the accumulation and discharge of metals in various trophic levels of the environment. Due to these concerns, it is important to understand the toxicity mechanisms of metals and metallic nanoparticles before they lead to unhealthy effects on human health. In this review paper, we specifically focus on the effect of metal copper and CuNPs on different fish organs under different physiochemical parameters of various water bodies. Nowadays, different forms of copper have distinctive and specific usages, e.g., copper sulfate is a well-established pesticide which is used to control the growth of algae in lakes and ponds. Deactivating the fungi enzymes prevents fungal spores from germinating. This process of deactivation is achieved via the free cupric ions, which are established as the most toxic forms of copper. Complexes of copper with other ligands may or may not be bioavailable for use in aquatic organisms. On the other hand, CuNPs have shown cost-effectiveness and numerous promising uses, but the toxicity and availability of copper in a nanoparticle form is largely unknown, Additionally, physiochemical factors such as the hardness of the water, alkalinity, presence of inorganic and organic ligands, levels of pH, and temperature in various different water bodies affect the toxicity caused by copper and CuNPs. However, comprehensive knowledge and data regarding the pattern of toxicity for copper metal ions and CuNPs in marine organisms is still limited. In this review, we carry out a critical analysis of the availability of the toxicological profiles of copper metal ions and CuNPs for different fishes in order to understand the toxicity mechanisms of copper and CuNPs. We believe that this review will provide valuable information on the toxicological profile of copper, which will further help in devising safe guidelines for the usage of copper and CuNPs in a sustainable manner. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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