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Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition

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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: 15 November 2026 | Viewed by 10952

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Prof. Dr. David B. Alexander

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Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
Interests: cancer; inflammatory; carcinogens; inflammatory bowel diseases
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Dear Colleagues,

The extraordinary physicochemical properties of engineered nanomaterials and nanoparticles (herein referred to as NMPs) gives them a multitude of uses. Different NMPs can also have different toxicities. NMPs are very lightweight and easily inhaled. The biopersistence of inhaled NMPs can lead to persistent inflammation in the lungs, which in turn can lead to respiratory disorders and neoplasia. In addition to inhalation, humans can be exposed to NMPs via dermal contact and via the ingestion of NMPs in food and water. The risks to human health and the environment posed by NMPs are of concern because of their numerous industrial applications and the use of NMPs in a wide range of commercial products. However, the elimination of currently used NMPs would likely have an immense negative impact on human society. Nonetheless, the risks posed by NMPs cannot be ignored. Therefore, hazardous NMPs need to be identified, and risk assessment studies need to be carried out. If risk assessments determine that an NMP can be safely used, appropriate regulations should be put into place that ensure the safe manufacture and use of the NMP.

The goal of this Special Issue is to highlight the latest research on the toxicology and safe use of nanomaterials and nanoparticles. We invite original research articles and reviews on human exposure to nanomaterials and nanoparticles, the toxicities of different types of nanomaterials and nanoparticles, and workplace and user safety measures that can be applied to ensure the safe manufacture and use of these extremely valuable materials.

Dr. David B. Alexander
Guest Editor

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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.

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Keywords

inhalation toxicity of nanomaterials/nanoparticles
dermal toxicity of nanomaterials/nanoparticles
oral toxicity of nanomaterials/nanoparticles
biopersistance of nanomaterials/nanoparticles
human exposure to nanomaterials/nanoparticles
workplace safety
users’ safety

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Related Special Issue

Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials in Nanomaterials (8 articles)

Published Papers (8 papers)

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Research

Jump to: Review

16 pages, 1127 KB

Open AccessArticle

Comparative Gene Expression Analysis of Malignant Mesothelioma and Lung Adenocarcinomas Induced by Multi-Walled Carbon Nanotube-7 and Double-Walled Carbon Nanotubes in Rats: Distinct Molecular Signatures and Canonical Pathways

by Min Gi, Shugo Suzuki, Dina Mourad Saleh, Omnia Hosny Mohamed Ahmed, William T. Alexander, Masaki Fujioka, Arpamas Vachiraarunwong, Runjie Guo, Guiyu Qiu, Ikue Noura, Anna Kakehashi, Xiao-Li Xie, Shuji Tsuruoka, Akihiko Hirose, Aya Naiki-Ito, Hiroyuki Tsuda and Hideki Wanibuchi

Nanomaterials 2025, 15(23), 1806; https://doi.org/10.3390/nano15231806 - 29 Nov 2025

Viewed by 714

Abstract

Although numerous experimental studies have demonstrated the carcinogenic potential of multi-walled carbon nanotubes (MWCNTs) in lungs, the underlying molecular mechanisms—especially gene expression changes associated with different tumor types—remain poorly characterized. To elucidate the molecular signatures associated with MWCNT-induced carcinogenesis, we performed microarray-based gene expression profiling of rat lung tumors induced by MWCNT-7, including both adenocarcinoma (ADC) and malignant mesothelioma (MM), as well as ADCs induced by two types of double-walled CNTs (DWCNTs) differing in fiber length (1.5 µm and 7 µm). Hierarchical clustering revealed that the MWCNT-7-induced MM exhibited a gene expression profile distinct from the ADCs. The ADCs induced by the DWCNTs and the ADC induced by MWCNT-7 shared several pathways that were distinct from those of the MWCNT-7 induced MM. The distinct pathways upregulated in the ADCs versus the MM support the conclusion that MWCNT-induced ADCs arise through distinct biological mechanisms compared to MWCNT-induced MMs and identified tumor-type-specific biomarker candidates: complement factor I (CFI) and secreted phosphoprotein 1 (SPP1) for ADCs, and fibronectin 1 (FN1) for MM. In addition, the gene expression profiles of the ADCs induced by the three fiber types indicate that both types of thin flexible DWCNTs used in the present study promoted a number of carcinogenic pathways in the rat lung that were also promoted by MWCNT-7, which is a class 2B carcinogen. These results support the conclusion that DWCNTs are carcinogenic in the rat lung and highlight the importance of further assessments of the potential lung carcinogenicity of inhaled thin flexible CNTs. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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21 pages, 10248 KB

Open AccessArticle

Comparative Carcinogenicity of Double-Walled Carbon Nanotubes of Different Lengths Administered by Intratracheal Installation into Rat Lungs

by Omnia Hosny Mohamed Ahmed, Dina Mourad Saleh, William T. Alexander, Hiroshi Takase, Yuhji Taquahashi, Motoki Hojo, Ai Maeno, Katsumi Fukamachi, Min Gi, Akihiko Hirose, Shuji Tsuruoka, Satoru Takahashi, Hiroyuki Tsuda and Aya Naiki-Ito

Nanomaterials 2025, 15(18), 1402; https://doi.org/10.3390/nano15181402 - 11 Sep 2025

Cited by 1 | Viewed by 961

Abstract

We previously carried out an in vivo 2-year study to assess the potential toxicity/carcinogenicity of double-walled carbon nanotubes (DWCNTs) in a rat lung. We found that administration of DWCNTs by intratracheal–intrapulmonary spraying (TIPS) at a dose of 0.5 mg/rat induced the development of lung tumors in 7 of 24 treated rats while 1 of 21 untreated rats and 1 of 25 vehicle treated rats developed lung tumors. In the current study, we administered DWCNTs of different lengths, 1.5 µm, 7 µm, and 15 µm, to rats by TIPS to investigate the possible effect of the length of this thin, flexible CNT on toxicity/carcinogenicity in rat lungs. Rats were administered DWCNTs with lengths of 1.5 µm (D1.5), 7 µm (D7), and 15 µm (D15) by TIPS once every other day over the course of two weeks for a total of eight administrations. The total dose administered was approximately 22 × 10¹² fibers per rat, corresponding to 0.0504 mg for D1.5, 0.232 mg for D7, and 0.504 mg for D15. Another group of rats was administered 0.5 mg MWCNT-7, a known carcinogen. Animals were killed at weeks 6 and 104 (4 and 102 weeks after the final TIPS administration). The mean survival time of the rats in the untreated, vehicle, D1.5, D7, and D15 groups was 99 to 104 weeks. One rat in the D1.5 group and one rat in the D15 group died before week 75. The remaining rats in the untreated, vehicle, D1.5, D7, and D15 groups were included in the final assessment of lung toxicity/carcinogenicity. In contrast, 11 rats in the MWCNT-7 group died before week 75 due to the development of malignant mesothelioma. Due to the much shorter survival time of the rats treated with MWCNT-7, accurate assessment of lung proliferative lesions in this group was not possible. At week 6, an increase in alveolar macrophages and granulation tissue foci in the alveoli was observed in all DWCNT administered groups. The alveolar epithelial cell PCNA index was also significantly increased in the D7 and D15 groups. Increases in alveolar macrophages, granulation tissue foci, and the alveolar epithelial cell PCNA index were observed in all DWCNT-treated groups at the final sacrifice. The incidences of lung tumors were 0/13, 0/12, 4/12, 3/8, and 2/10 in the untreated, vehicle, D1.5, D7, and D15 groups, respectively. In agreement with our previous study, the DWCNTs tested in the present study were carcinogenic in the rat lung. In addition, we present evidence that DWCNT fiber length may possibly have an effect on DWCNT-induced carcinogenicity in rat lungs. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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16 pages, 2807 KB

Open AccessArticle

Evaluating the Impact of Carbon Nanoparticles on the Interfacial Properties of the Pulmonary Surfactant Film

by Yingxue Geng, Qun Zhao, Junfeng Wang, Yan Cao, Yunshan Wang, Wenshi Gou, Linfeng Zhang and Senlin Tian

Nanomaterials 2025, 15(16), 1244; https://doi.org/10.3390/nano15161244 - 14 Aug 2025

Cited by 1 | Viewed by 897

Abstract

The interaction between carbon nanoparticles (CNs) and Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a model pulmonary surfactant (PS) film was studied to shed light on the physicochemical bases underlying the potential adverse effects associated with pollutant inhalation. The results indicated that the surface pressure–area isotherms of the DPPC monolayers shifted toward lower molecular areas, and the compression modulus was reduced in the presence of CNs, hindering the ability of the DPPC monolayers to reduce the surface tension. The relaxation process of the DPPC monolayers were influenced, and the surface morphology and the continuity of the monolayers were destroyed by the penetration of CNs into the DPPC monolayers. The molecular dynamics simulation revealed that particle incorporation into the DPPC monolayers reduced the packing density of the DPPC molecules, worsening the mechanical performance of the monolayers. This effect was attributed to the strong binding trend between the CNs and the DPPC molecules. These results demonstrated that CNs could alter the relaxation mechanisms of the PS film, and this may cause a modification of the inhaled particle transport at the PS film and contribute to adverse health effects in the respiratory system of workers involved in the CN production process. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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16 pages, 5821 KB

Open AccessArticle

Synthesis, Characterization, and Toxicity Evaluation of Size-Dependent Iron-Based Metal–Organic Frameworks

by Zhang Liu, Huaiyu Deng, Yuanzhi Zheng, Yuan Tian, Yanting Zhang, Renz Marion Garcia, Sheena Anne Henson Garcia and King Lun Yeung

Nanomaterials 2025, 15(12), 927; https://doi.org/10.3390/nano15120927 - 14 Jun 2025

Cited by 9 | Viewed by 2210

Abstract

Iron-based metal–organic frameworks (Fe-MOFs) are promising for biomedical and environmental applications due to their porosity, tunable chemistry, and biocompatibility. This study examines how particle size, morphology, and ligand composition affect the properties and cytotoxicity of MIL-101(Fe) and MIL-88A. MIL-101(Fe) (octahedral) and MIL-88A (rod-like) were synthesized with a controlled size (~200 nm to ~5 μm). Both showed a high crystallinity and stability. Cytotoxicity assays in A549 cells revealed size- and structure-dependent effects: smaller particles of MIL-88A caused greater toxicity (32.5% viability) than MIL-101(Fe) (66.1% viability at 100 μg/mL), while larger particles were less toxic. MIL-88A also induced higher reactive oxidative species (ROS) levels and degraded more rapidly, releasing more Fe ions. Toxicity predication analysis indicated the higher inherent toxicity of MIL-88A’s ligand (fumaric acid) compared to MIL-101(Fe)’s terephthalic acid. These results demonstrate that structural and chemical factors collectively influence Fe-MOFs’ biocompatibility and highlight the importance of rational design for safer MOF applications. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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23 pages, 2027 KB

Open AccessArticle

Development and Evaluation of a Novel Self-Etch Dental Adhesive Incorporating Graphene Oxide–Zirconia (GO-ZrO₂) and Hydroxyapatite–Zinc (HA-Zn) for Enhanced Bond Strength, Biocompatibility, and Long-Term Stability

by Norbert Erich Serfözö, Marioara Moldovan, Doina Prodan and Nicoleta Ilie

Nanomaterials 2025, 15(11), 803; https://doi.org/10.3390/nano15110803 - 27 May 2025

Cited by 3 | Viewed by 1522

Abstract

The aim of this study was to develop an experimental self-etch dental adhesive (SE) by synthesizing graphene oxide–functionalized zirconia (GO-ZrO₂) and hydroxyapatite–functionalized zinc (HA-Zn) as inorganic powders together with bis-GMA _(0–2) (bisphenol A-glycidyl methacrylate) oligomers as main components of the organic matrix. The adhesive was compared to the current gold standard adhesive Clearfill SE Bond 2 (CSE) using cytotoxicity assays, shear bond strength (SBS) tests, and resin–dentin interface analyses. Cytotoxicity assays with human gingival fibroblasts (HGF-1) revealed reduced cell viability at early time points but indicated favourable biocompatibility and potential cell proliferation at later stages. SBS values for the experimental adhesive were comparable to CSE after 24 h of storage while aging did not significantly affect its bond strength. However, SBS exhibited more consistent resin tag formation and higher Weibull modulus values post-aging. A scanning electron microscopy (SEM) analysis highlighted differences in resin tag formation, suggesting the experimental adhesive relies more on chemical bonding than micromechanical interaction. The experimental adhesive demonstrated promising potential clinical properties and bond durability due to the integration of GO-ZrO₂ and HA-Zn fillers into the adhesive. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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Review

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21 pages, 1271 KB

Open AccessReview

Nano- and Microplastics in the Cardiovascular System: Current Insights and Biological Implications

by Mario Cristina, Manuel Belli, Anna Baroni, Chantalle Moulton, Emily Carinci, Marta Gatti, Ennio Tasciotti, Matteo Antonio Russo, Patrizia Russo and Luigi Sansone

Nanomaterials 2026, 16(10), 589; https://doi.org/10.3390/nano16100589 - 12 May 2026

Viewed by 476

Abstract

Micro- and nanoplastics (MNPs) are ubiquitous environmental pollutants recognized as emerging and relevant risk factors for numerous human diseases, including cardiovascular diseases. MNPs enter the human body through ingestion, inhalation, and dermal penetration, and their toxicity varies according to size, shape, and chemical composition, most notably between microplastics (>1 µm) and nanoplastics (<1 µm), which differ in cellular uptake mechanisms and biodistribution. Recent evidence has confirmed their presence in cardiac and vascular tissues, raising significant concerns about their potential impact on human health. This review summarizes current knowledge on MNP exposure sources, physicochemical properties, and systemic bioavailability, with a particular emphasis on the mechanisms of transport that facilitate their deposition within the myocardium and vasculature. It further addresses a broad spectrum of cardiotoxic effects, including oxidative stress, mitochondrial injury, immune activation, ion channel disruption, cell death, and fibrosis. Endothelial dysfunction, vascular injury, and pro-atherogenic activity are also discussed. In addition to outlining existing detection techniques and emerging in vitro models, the review highlights initial steps toward the development of preventive strategies. Concluding with key knowledge gaps and future research directions, this article underscores the urgent need for standardized measurement tools, deeper insights into damage mechanisms, and clinical interventions to prevent MNP-induced cardiovascular diseases. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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25 pages, 6509 KB

Open AccessReview

The Pneumoconiosis Renaissance: Revisiting the Pulmonary Pathology of Poorly Soluble Low Toxicity Particles: Insights from Rodent Inhalation Studies on Titanium Dioxide Nanoparticles

by Shotaro Yamano, Dirk Schaudien and Yumi Umeda

Nanomaterials 2026, 16(4), 230; https://doi.org/10.3390/nano16040230 - 11 Feb 2026

Viewed by 1220

Abstract

Historically, the toxicological evaluation of poorly soluble low toxicity particles (PSLTs), such as titanium dioxide nanoparticles (TiO₂ NPs), distinct from conventional pigment-grade TiO₂, has focused on carcinogenicity and lung overload, leaving their pathological function in the development of pneumoconiosis undefined. In this study, we initiated a “Pneumoconiosis Renaissance”, redefining the human “Gold Standard” of pneumoconiosis pathology as a primarily interstitial “Dust Macule (DM) to Mixed Dust Fibrosis (MDF) axis”. In contrast, rats developed a species-specific “Airspace-Dominant Phenotype” (Pulmonary Dust Foci) driven by airspace stagnation. Integrating recent continuous inhalation exposure and recovery after inhalation exposure studies, we demonstrate that this overwhelming alveolar pathology in rats acts as a “Biological Mask”, physically superimposing upon and obscuring human-relevant interstitial sequestration. Crucially, however, extended recovery periods can unmask these interstitial events, revealing the true underlying pathology. We propose that future risk assessments and Adverse Outcome Pathways (AOPs) must incorporate spatial resolution. By rigorously segregating sensitive rat-specific airspace events from human-relevant interstitial remodeling, we can accurately bridge the interspecies gap. This review argues that rather than discarding the rat model, we must learn to decode it—using spatial distinctions to filter the airspace mask and evaluate the true interstitial risk of inhaled biodurable particles. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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50 pages, 4429 KB

Open AccessReview

Nanotoxicity of Porous Silica Nanoparticles: Physicochemical Properties and Mechanistic Cellular Endpoints

by Trisha Patel, Callum Clipstone, Umakhanth Venkatraman Girija, Zeeshan Ahmad and Neenu Singh

Nanomaterials 2025, 15(23), 1766; https://doi.org/10.3390/nano15231766 - 25 Nov 2025

Cited by 3 | Viewed by 1988

Abstract

This review provides a comprehensive overview of the fundamental aspects of nanoparticles (NPs), emphasizing their physicochemical properties and biological interactions, with particular focus on porous silica nanoparticles (PSNs). The review provides information on the Safe-by-design (SbD) S.A.F.E. (Standardised characterization, Assessment of biocompatibility, Facilitation of toxicity and exposure routes and Evaluation of clinical translation) framework. It discusses critical factors influencing NP toxicity and cellular uptake, including particle size, shape, pore size, surface charge, surface functionalisation, and crystallinity. The review also examines exposure routes of NPs—inhalation, dermal, oral, systemic and mucosal—and their subsequent biological effects. A key section is dedicated to the formation of the protein corona, a critical determinant of NP fate in biological systems, and its influence on circulation time, immune clearance and cellular responses. Particular attention is given to assessing the biological interactions of the PSNs and the mechanisms underlying PSN-induced cytotoxicity and genotoxicity, with a focus on the assays commonly employed to evaluate these effects. The review explores the use of gene expression profiling as a powerful tool to elucidate the molecular mechanisms underlying nanoparticle-induced cellular changes. This review aims to provide an integrated perspective on the SbD considerations and safety implications of nanomaterials. It highlights the need for a deeper understanding of complex biological interactions to establish SbD principles and enable the translation of PSNs into clinical applications. Finally, current regulatory frameworks and guidelines for testing nanomaterials, including PSNs, that support their safe and sustainable development are discussed. Full article

(This article belongs to the Special Issue Safety and Toxicity of Carbon Nanotubes, Nanoparticles and Other Nanomaterials: 2nd Edition)

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