**Toxicology and Biocompatibility of Nanomaterials**

Editors

**Carsten Weiss Silvia Diabat´e**

MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin


*Editorial Office* MDPI St. Alban-Anlage 66 4052 Basel, Switzerland

This is a reprint of articles from the Special Issue published online in the open access journal *Nanomaterials* (ISSN 2079-4991) (available at: www.mdpi.com/journal/nanomaterials/special issues/toxic biocompt).

For citation purposes, cite each article independently as indicated on the article page online and as indicated below:

LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. *Journal Name* **Year**, *Volume Number*, Page Range.

**ISBN 978-3-0365-2739-0 (Hbk) ISBN 978-3-0365-2738-3 (PDF)**

© 2021 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications.

The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.

## **Contents**


Reprinted from: *Nanomaterials* **2020**, *10*, 1021, doi:10.3390/nano10061021 . . . . . . . . . . . . . . **89**

#### **Anna von Mikecz and Tamara Schikowski**

Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases Reprinted from: *Nanomaterials* **2020**, *10*, 1349, doi:10.3390/nano10071349 . . . . . . . . . . . . . . **107**

#### **Svenja Siemer, D´esir´ee W ¨unsch, Aya Khamis, Qiang Lu, Arnaud Scherberich, Miriam Filippi, Marie Pierre Krafft, Jan Hagemann, Carsten Weiss, Guo-Bin Ding, Roland H. Stauber and Alena Gribko**

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy

Reprinted from: *Nanomaterials* **2020**, *10*, 383, doi:10.3390/nano10020383 . . . . . . . . . . . . . . . **117**

## **About the Editors**

#### **Carsten Weiss**

Carsten Weiss is a research group leader at the Institute of Chemical and Biological Systems at the Karlsruhe Institute of Technology (KIT). Upon completing his PhD in Biology at the University of Karlsruhe, he gained practical experience in the field of Molecular Toxicology, including the completion of several post-doctoral fellowships in Germany and the USA. His main research addresses the role of signaling in response to environmental particulate matter and genotoxins. Dr. Weiss was and still is involved in numerous national and European projects concerned with safety assessment and the molecular action of (nano)materials and genotoxins.

#### **Silvia Diabat ´e**

Dr. Silvia Diabate is a biologist by training and has extensive experience in the toxicology ´ of combustion-derived particles and nanoparticles, with special emphasis on inflammatory and anti-oxidative processes in lung cells. Together with her colleagues at KIT, she developed in vitro assays for investigating the potential toxicity of aerosols in cell cultures after exposure at the air–liquid interface.

## **Preface to "Toxicology and Biocompatibility of Nanomaterials"**

With great pleasure, we served as guest editors for this Special Issue entitled "Toxicology and Biocompatibility of Nanomaterials". Although the benefits of nanomaterials are obvious, concern has also been raised about such materials being inhaled, ingested, applied to the skin, or even released into the environment, potentially inducing adverse effects. In this book, some timely original research articles as well as reviews address various aspects of this interesting topic. Once more, we thank all of the authors for their valuable contributions, and the many constructive reviewers and the editorial team who helped to bring this Special Issue to fruition. We hope that a broad readership will enjoy this book.

> **Carsten Weiss, Silvia Diabat ´e** *Editors*

## *Editorial* **Toxicology and Biocompatibility of Nanomaterials**

**Carsten Weiss \* and Silvia Diabaté**

Institute of Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany; silvia.diabate@kit.edu

**\*** Correspondence: carsten.weiss@kit.edu

It is our great pleasure to introduce this Special Issue entitled "Toxicology and Biocompatibility of Nanomaterials". As the understanding of materials at the nanoscale and the ability to control their structure improves, a wide range of nanomaterials (NMs) with novel characteristics and applications are being fabricated for electronics, engineering, and, more recently, biomedical research applications. Although the technological and economic benefits of NMs are obvious, concern has also been raised that the very same properties, which enable a variety of novel applications, might have adverse effects if such a material is inhaled, ingested, applied to the skin or even released into the environment [1]. These concerns have led to an increasing discussion worldwide about possible regulatory policies for NMs. Therefore, there is a clear need to establish convincing scientific knowledge to assess the impact of NMs 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, as outlined in our first Special Issue on the topic one decade ago [2]. Meanwhile, the field of nanotoxicology has come of age, and is an established discipline in toxicology.

This Special Issue comprises six research articles and two timely reviews and covers research in the field of nanotoxicology, with a particular interest in molecular mechanism of action as well as the safe-by-design concept, i.e., the synthesis of biocompatible nanomaterials. Additionally, the impact of the biomolecular corona, which is the interaction of biomolecules with the NM surface, on toxicity and biocompatibility, is addressed.

The first study addresses the effects of ZnO NMs on blood glucose levels in healthy and diabetic rats and discusses potential clinical applications [3]. The following articles are mainly in vitro studies with a focus on mechanisms of NM toxicity. Macrophages are important targets of NMs; therefore, the understanding of molecular initiating events is of high relevance. A series of TiO<sup>2</sup> NMs with different characteristics were studied in rat alveolar macrophages and activation of the NLRP3 inflammasome is presented, highlighting the importance of case-to-case studies for proper hazard assessment [4]. In murine macrophages, the poorly understood mixture effects of co-pollutants and NMs has been investigated [5]. The authors demonstrate synergistic activities of silica NMs and genotoxic agents, thus reinforcing the notion that there is an urgent need to pay more attention to mixture effects in the future. Apart from the innate immune system, the gastrointestinal tract is an important target tissue. Therefore, the toxicity of silica NMs is explored in gastrointestinal cells [6], specifically in the presence or absence of serum, because the biomolecular corona has previously been shown to critically determine detrimental effects in other cell types [7]. Although in the presence of serum even proproliferative effects have been shown in gastric cells [8], in the absence of serum, silica NMs potently induce cell death in colon carcinoma cells; however, this is independent of the key regulators p53 and BAX, suggesting the potential for their further development as anticancer nanodrugs [6]. Although the field of nanotoxicology has matured and solved most of the initial technical problems and challenges, there are still issues which hamper proper hazard assessment. These include, but are not limited to, the reproducible

**Citation:** Weiss, C.; Diabaté, S. Toxicology and Biocompatibility of Nanomaterials. *Nanomaterials* **2021**, *11*, 3110. https://doi.org/10.3390/ nano11113110

Received: 11 November 2021 Accepted: 17 November 2021 Published: 18 November 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

synthesis of NMs with clearly characterized physico-chemical properties [9], as well as the establishment of more physiologically relevant test systems [10] and standard operating procedures for toxicity testing to provide comparable results across laboratories. Thus, fifteen European laboratories performed an inter-laboratory comparison to assess the toxicity of polystyrene NMs with the widely used MTS assay and provide guidance on how to improve reliable testing [11]. Finally, the interactions of CeO<sup>2</sup> and TiO<sup>2</sup> NMs and algae were addressed in an ecotoxicity study, and the importance of the adherence of NMs to the test organism was identified as an important parameter to predict toxicity [12].

Two reviews conclude this Special Issue. The first summarizes our knowledge of airborne NMs and their potential adverse effects on the nervous system with a specific focus on neurodegenerative diseases [13]. The final contribution provides a fresh outlook on positive aspects of NM actions in biological systems, i.e., their use in medicine as tools to diagnose and treat cancer [14].

In conclusion, we would like to thank all the authors for their interesting and excellent contributions, and the many constructive reviewers and the editorial team who helped to bring this Special Issue to fruition. We hope that a broad readership will enjoy this Special Issue.

**Author Contributions:** C.W. prepared the original draft, which was reviewed and edited by S.D. All authors have read and agreed to the published version of the manuscript.

**Funding:** This article received no external funding.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We are grateful to Mirabelle Wang from *Nanomaterials* for her continuous support. We are grateful to all the authors for submitting their studies to the present Special Issue and for its successful completion. We deeply acknowledge the *Nanomaterials* reviewers for enhancing the quality and impact of all submitted papers.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


*Communication*
