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Nanomaterials
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Toxicology and Biocompatibility of Nanomaterials
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Toxicology and Biocompatibility of Nanomaterials

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

Deadline for manuscript submissions: closed (25 June 2020) | Viewed by 37046

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Carsten Weiss

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Guest Editor
Institute of Biological and Chemical Systems–Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Hermann‐von‐Helmholtz‐Platz 1, 76344 Eggenstein‐Leopoldshafen, Germany
Interests: nanotoxicology; nanomedicine; molecular toxicology
Special Issues, Collections and Topics in MDPI journals
Dr. Silvia Diabaté

E-Mail Website
Guest Editor
Institute of Biological and Chemical Systems – Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Hermann‐von‐Helmholtz‐Platz 1, 76344 Eggenstein‐Leopoldshafen, Germany
Interests: nanotoxicology; nanomedicine; molecular toxicology

Special Issue Information

Dear Colleagues,

As the understanding of materials at the nanoscale and the ability to control their structure improves, a wide range of nanoparticles (NPs) with novel characteristics and applications are fabricated for, e.g., electronics, engineering and, more recently, in biomedical research. Although the technological and economic benefits of NPs are obvious, concern has also been raised that the very same properties, which open a variety of novel applications, might have adverse effects if such material is inhaled, ingested, applied to the skin or even released into the environment. These concerns have led to an increasing discussion worldwide about possible regulatory policies for NPs. Therefore, there is clearly the need to establish convincing scientific knowledge to assess the impact of NPs on human health and the ecosystem. These questions can only be tackled by collaborative research at the interface of engineering, physics, chemistry, toxicology, and biology.
This Special Issue will cover research in the field of nanotoxicology with a special interest in molecular mechanism of action as well as the safe-by-design concept, i.e., the synthesis of biocompatible nanomaterials. Further, the impact of the bio-corona, that is, the interaction of biomolecules with the NP surface, on toxicity and biocompatibility will be addressed. We welcome submission of reviews, original research articles, and communications.

Dr. Carsten Weiss
Dr. Silvia Diabaté
Guest Editors

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

  • nano(eco)toxicology
  • nanomedicine
  • biocompatibility
  • bio-corona
  • toxicity pathways

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Published Papers (9 papers)

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Editorial

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3 pages, 181 KiB  
Editorial
Toxicology and Biocompatibility of Nanomaterials
by Carsten Weiss and Silvia Diabaté
Nanomaterials 2021, 11(11), 3110; https://doi.org/10.3390/nano11113110 - 18 Nov 2021
Cited by 1 | Viewed by 1706
Abstract
It is our great pleasure to introduce this Special Issue entitled “Toxicology and Biocompatibility of Nanomaterials” [...] Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)

Research

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10 pages, 1438 KiB  
Communication
Zinc Oxide Nanoparticles Induce an Adverse Effect on Blood Glucose Levels Depending On the Dose and Route of Administration in Healthy and Diabetic Rats
by Adolfo Virgen-Ortiz, Alejandro Apolinar-Iribe, Irene Díaz-Reval, Hortensia Parra-Delgado, Saraí Limón-Miranda, Enrique Alejandro Sánchez-Pastor, Luis Castro-Sánchez, Santos Jesús Castillo, Adan Dagnino-Acosta, Edgar Bonales-Alatorre and Alejandrina Rodríguez-Hernández
Nanomaterials 2020, 10(10), 2005; https://doi.org/10.3390/nano10102005 - 12 Oct 2020
Cited by 14 | Viewed by 3206
Abstract
Different studies in experimental diabetes models suggest that zinc oxide nanoparticles (ZnONPs) are useful as antidiabetic agents. However, this evidence was performed and measured in long-term treatments and with repeated doses of ZnONPs. This work aimed to evaluate the ZnONPs acute effects on [...] Read more.
Different studies in experimental diabetes models suggest that zinc oxide nanoparticles (ZnONPs) are useful as antidiabetic agents. However, this evidence was performed and measured in long-term treatments and with repeated doses of ZnONPs. This work aimed to evaluate the ZnONPs acute effects on glycemia during the next six h after an oral or intraperitoneal administration of the treatment in healthy and diabetic rats. In this study, the streptozotocin-nicotinamide intraperitoneal administration in male Wistar rats were used as a diabetes model. 10 mg/kg ZnONPs did not modify the baseline glucose in any group. Nevertheless, the ZnONPs short-term administration (100 mg/kg) induced a hyperglycemic response in a dose and route-dependent administration in healthy (130 ± 2 and 165 ± 10 mg/dL with oral and intraperitoneal, respectively) and diabetic rats (155 ± 2 and 240 ± 20 mg/dL with oral, and intraperitoneal, respectively). The diabetic rats were 1.5 fold more sensitive to ZnONPs effect by the intraperitoneal route. In conclusion, this study provides new information about the acute response of ZnONPs on fasting glycemia in diabetic and healthy rat models; these data are essential for possible future clinical approaches. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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18 pages, 1844 KiB  
Article
Evaluation of the NLRP3 Inflammasome Activating Effects of a Large Panel of TiO2 Nanomaterials in Macrophages
by Julia Kolling, Jonas Tigges, Bryan Hellack, Catrin Albrecht and Roel P. F. Schins
Nanomaterials 2020, 10(9), 1876; https://doi.org/10.3390/nano10091876 - 19 Sep 2020
Cited by 15 | Viewed by 3402
Abstract
TiO2 nanomaterials are among the most commonly produced and used engineered nanomaterials (NMs) in the world. There is controversy regarding their ability to induce inflammation-mediated lung injuries following inhalation exposure. Activation of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome [...] Read more.
TiO2 nanomaterials are among the most commonly produced and used engineered nanomaterials (NMs) in the world. There is controversy regarding their ability to induce inflammation-mediated lung injuries following inhalation exposure. Activation of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome and subsequent release of the cytokine interleukin (IL)-1β in pulmonary macrophages has been postulated as an essential pathway for the inflammatory and associated tissue-remodeling effects of toxic particles. Our study aim was to determine and rank the IL-1β activating properties of TiO2 NMs by comparing a large panel of different samples against each other as well as against fine TiO2, synthetic amorphous silica and crystalline silica (DQ12 quartz). Effects were evaluated in primary bone marrow derived macrophages (BMDMs) from NALP3-deficient and proficient mice as well as in the rat alveolar macrophage cell line NR8383. Our results show that specific TiO2 NMs can activate the inflammasome in macrophages albeit with a markedly lower potency than amorphous SiO2 and quartz. The heterogeneity in IL-1β release observed in our study among 19 different TiO2 NMs underscores the relevance of case-by-case evaluation of nanomaterials of similar chemical composition. Our findings also further promote the NR8383 cell line as a promising in vitro tool for the assessment of the inflammatory and inflammasome activating properties of NMs. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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20 pages, 1119 KiB  
Article
Improving Quality in Nanoparticle-Induced Cytotoxicity Testing by a Tiered Inter-Laboratory Comparison Study
by Inge Nelissen, Andrea Haase, Sergio Anguissola, Louise Rocks, An Jacobs, Hanny Willems, Christian Riebeling, Andreas Luch, Jean-Pascal Piret, Olivier Toussaint, Bénédicte Trouiller, Ghislaine Lacroix, Arno C. Gutleb, Servane Contal, Silvia Diabaté, Carsten Weiss, Tamara Lozano-Fernández, África González-Fernández, Maria Dusinska, Anna Huk, Vicki Stone, Nilesh Kanase, Marek Nocuń, Maciej Stępnik, Stefania Meschini, Maria Grazia Ammendolia, Nastassja Lewinski, Michael Riediker, Marco Venturini, Federico Benetti, Jan Topinka, Tana Brzicova, Silvia Milani, Joachim Rädler, Anna Salvati and Kenneth A. Dawsonadd Show full author list remove Hide full author list
Nanomaterials 2020, 10(8), 1430; https://doi.org/10.3390/nano10081430 - 22 Jul 2020
Cited by 13 | Viewed by 5276
Abstract
The quality and relevance of nanosafety studies constitute major challenges to ensure their key role as a supporting tool in sustainable innovation, and subsequent competitive economic advantage. However, the number of apparently contradictory and inconclusive research results has increased in the past few [...] Read more.
The quality and relevance of nanosafety studies constitute major challenges to ensure their key role as a supporting tool in sustainable innovation, and subsequent competitive economic advantage. However, the number of apparently contradictory and inconclusive research results has increased in the past few years, indicating the need to introduce harmonized protocols and good practices in the nanosafety research community. Therefore, we aimed to evaluate if best-practice training and inter-laboratory comparison (ILC) of performance of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay for the cytotoxicity assessment of nanomaterials among 15 European laboratories can improve quality in nanosafety testing. We used two well-described model nanoparticles, 40-nm carboxylated polystyrene (PS-COOH) and 50-nm amino-modified polystyrene (PS-NH2). We followed a tiered approach using well-developed standard operating procedures (SOPs) and sharing the same cells, serum and nanoparticles. We started with determination of the cell growth rate (tier 1), followed by a method transfer phase, in which all laboratories performed the first ILC on the MTS assay (tier 2). Based on the outcome of tier 2 and a survey of laboratory practices, specific training was organized, and the MTS assay SOP was refined. This led to largely improved intra- and inter-laboratory reproducibility in tier 3. In addition, we confirmed that PS-COOH and PS-NH2 are suitable negative and positive control nanoparticles, respectively, to evaluate impact of nanomaterials on cell viability using the MTS assay. Overall, we have demonstrated that the tiered process followed here, with the use of SOPs and representative control nanomaterials, is necessary and makes it possible to achieve good inter-laboratory reproducibility, and therefore high-quality nanotoxicological data. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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17 pages, 3114 KiB  
Article
Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents
by Fanny Dussert, Pierre-Adrien Arthaud, Marie-Edith Arnal, Bastien Dalzon, Anaëlle Torres, Thierry Douki, Nathalie Herlin, Thierry Rabilloud and Marie Carriere
Nanomaterials 2020, 10(7), 1418; https://doi.org/10.3390/nano10071418 - 21 Jul 2020
Cited by 21 | Viewed by 4072
Abstract
Synthetic amorphous silica (SAS) is used in a plethora of applications and included in many daily products to which humans are exposed via inhalation, ingestion, or skin contact. This poses the question of their potential toxicity, particularly towards macrophages, which show specific sensitivity [...] Read more.
Synthetic amorphous silica (SAS) is used in a plethora of applications and included in many daily products to which humans are exposed via inhalation, ingestion, or skin contact. This poses the question of their potential toxicity, particularly towards macrophages, which show specific sensitivity to this material. SAS represents an ideal candidate for the adsorption of environmental contaminants due to its large surface area and could consequently modulate their toxicity. In this study, we assessed the toxicity towards macrophages and intestinal epithelial cells of three SAS particles, either isolated SiO2 nanoparticles (LS30) or SiO2 particles composed of agglomerated-aggregates of fused primary particles, either food-grade (E551) or non-food-grade (Fumed silica). These particles were applied to cells either alone or in combination with genotoxic co-contaminants, i.e., benzo[a]pyrene (B[a]P) and methane methylsulfonate (MMS). We show that macrophages are much more sensitive to these toxic agents than a non-differenciated co-culture of Caco-2 and HT29-MTX cells, used here as a model of intestinal epithelium. Co-exposure to SiO2 and MMS causes DNA damage in a synergistic way, which is not explained by the modulation of DNA repair protein mRNA expression. Together, this suggests that SiO2 particles could adsorb genotoxic agents on their surface and, consequently, increase their DNA damaging potential. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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18 pages, 7389 KiB  
Article
Attachment Efficiency of Nanomaterials to Algae as an Important Criterion for Ecotoxicity and Grouping
by Kerstin Hund-Rinke, Tim Sinram, Karsten Schlich, Carmen Nickel, Hanna Paula Dickehut, Matthias Schmidt and Dana Kühnel
Nanomaterials 2020, 10(6), 1021; https://doi.org/10.3390/nano10061021 - 27 May 2020
Cited by 13 | Viewed by 3167
Abstract
Engineered nanomaterials (ENMs) based on CeO2 and TiO2 differ in their effects on the unicellular green alga Raphidocelis subcapitata but these effects do not reflect the physicochemical parameters that characterize such materials in water and other test media. To determine whether [...] Read more.
Engineered nanomaterials (ENMs) based on CeO2 and TiO2 differ in their effects on the unicellular green alga Raphidocelis subcapitata but these effects do not reflect the physicochemical parameters that characterize such materials in water and other test media. To determine whether interactions with algae can predict the ecotoxicity of ENMs, we studied the attachment of model compounds (three subtypes of CeO2 and five subtypes of TiO2) to algal cells by light microscopy and electron microscopy. We correlated our observations with EC50 values determined in growth inhibition assays carried out according to the Organisation for Economic Co-operation and Development (OECD) test guideline 201. Light microscopy revealed distinct patterns of ENM attachment to algal cells according to the type of compound, with stronger interactions leading to greater toxicity. This was confirmed by electron microscopy, which allowed the quantitative assessment of particle attachment. Our results indicate that algal extracellular polymeric substances play an important role in the attachment of ENMs, influencing the formation of agglomerates. The attachment parameters in short-term tests predicted the toxicity of CeO2 and TiO2 ENMs and can be considered as a valuable tool for the identification of sets of similar nanoforms as requested by the European Chemicals Agency in the context of grouping and read-across. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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17 pages, 2170 KiB  
Article
Silica Nanoparticles Provoke Cell Death Independent of p53 and BAX in Human Colon Cancer Cells
by Susanne Fritsch-Decker, Zhen An, Jin Yan, Iris Hansjosten, Marco Al-Rawi, Ravindra Peravali, Silvia Diabaté and Carsten Weiss
Nanomaterials 2019, 9(8), 1172; https://doi.org/10.3390/nano9081172 - 16 Aug 2019
Cited by 16 | Viewed by 4388
Abstract
Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence [...] Read more.
Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (–NH2 and –COOH). Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the silica NPs promoted apoptosis and necrosis proportional to the administered specific surface area dose. Cytotoxicity of silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of caspases partially prevented silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug cisplatin, silica NPs induced cell death independent of the p53–BAX axis. In conclusion, silica NPs initiated cell death in colon cancer cells dependent on the specific surface area and presence of serum. Further studies in vivo are warranted to address potential cytotoxic actions in the gut epithelium. The unintended toxicity of silica NPs as observed here could also be beneficial. As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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Review

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10 pages, 1096 KiB  
Review
Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases
by Anna von Mikecz and Tamara Schikowski
Nanomaterials 2020, 10(7), 1349; https://doi.org/10.3390/nano10071349 - 10 Jul 2020
Cited by 18 | Viewed by 3975
Abstract
How the environment contributes to neurodegenerative diseases such as Alzheimer’s is not well understood. In recent years, science has found augmenting evidence that nano-sized particles generated by transport (e.g., fuel combustion, tire wear and brake wear) may promote Alzheimer’s disease (AD). Individuals residing [...] Read more.
How the environment contributes to neurodegenerative diseases such as Alzheimer’s is not well understood. In recent years, science has found augmenting evidence that nano-sized particles generated by transport (e.g., fuel combustion, tire wear and brake wear) may promote Alzheimer’s disease (AD). Individuals residing close to busy roads are at higher risk of developing AD, and nanomaterials that are specifically generated by traffic-related processes have been detected in human brains. Since AD represents a neurodegenerative disease characterized by amyloid protein aggregation, this review summarizes our current knowledge on the amyloid-generating propensity of traffic-related nanomaterials. Certain nanoparticles induce the amyloid aggregation of otherwise soluble proteins in in vitro laboratory settings, cultured neuronal cells and vertebrate or invertebrate animal models. We discuss the challenges for future studies, namely, strategies to connect the wet laboratory with the epidemiological data in order to elucidate the molecular bio-interactions of airborne nanomaterials and their effects on human health. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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28 pages, 3886 KiB  
Review
Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy
by Svenja Siemer, Désirée Wünsch, Aya Khamis, Qiang Lu, Arnaud Scherberich, Miriam Filippi, Marie Pierre Krafft, Jan Hagemann, Carsten Weiss, Guo-Bin Ding, Roland H. Stauber and Alena Gribko
Nanomaterials 2020, 10(2), 383; https://doi.org/10.3390/nano10020383 - 22 Feb 2020
Cited by 33 | Viewed by 6943
Abstract
Nanomaterials have great potential for the prevention and treatment of cancer. Circulating tumor cells (CTCs) are cancer cells of solid tumor origin entering the peripheral blood after detachment from a primary tumor. The occurrence and circulation of CTCs are accepted as a prerequisite [...] Read more.
Nanomaterials have great potential for the prevention and treatment of cancer. Circulating tumor cells (CTCs) are cancer cells of solid tumor origin entering the peripheral blood after detachment from a primary tumor. The occurrence and circulation of CTCs are accepted as a prerequisite for the formation of metastases, which is the major cause of cancer-associated deaths. Due to their clinical significance CTCs are intensively discussed to be used as liquid biopsy for early diagnosis and prognosis of cancer. However, there are substantial challenges for the clinical use of CTCs based on their extreme rarity and heterogeneous biology. Therefore, methods for effective isolation and detection of CTCs are urgently needed. With the rapid development of nanotechnology and its wide applications in the biomedical field, researchers have designed various nano-sized systems with the capability of CTCs detection, isolation, and CTCs-targeted cancer therapy. In the present review, we summarize the underlying mechanisms of CTC-associated tumor metastasis, and give detailed information about the unique properties of CTCs that can be harnessed for their effective analytical detection and enrichment. Furthermore, we want to give an overview of representative nano-systems for CTC isolation, and highlight recent achievements in microfluidics and lab-on-a-chip technologies. We also emphasize the recent advances in nano-based CTCs-targeted cancer therapy. We conclude by critically discussing recent CTC-based nano-systems with high therapeutic and diagnostic potential as well as their biocompatibility as a practical example of applied nanotechnology. Full article
(This article belongs to the Special Issue Toxicology and Biocompatibility of Nanomaterials)
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