NanotoxicologyPub Date : 2023-12-01Epub Date: 2023-12-14DOI: 10.1080/17435390.2023.2276413
Gary Hannon, Anna Bogdanska, Anna Keogh, Stephen P Finn, Oliviero L Gobbo, Adriele Prina-Mello
{"title":"Biodistribution and histological analysis of iron oxide-dextran nanoparticles in wistar rats.","authors":"Gary Hannon, Anna Bogdanska, Anna Keogh, Stephen P Finn, Oliviero L Gobbo, Adriele Prina-Mello","doi":"10.1080/17435390.2023.2276413","DOIUrl":"10.1080/17435390.2023.2276413","url":null,"abstract":"<p><p>Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles <i>in vivo</i> and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mg<sub>Fe</sub>/kg, 45 mg<sub>Fe</sub>/kg and 60 mg<sub>Fe</sub>/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"562-580"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-12-01Epub Date: 2024-01-18DOI: 10.1080/17435390.2023.2293144
Amina Kunovac, Quincy A Hathaway, Dharendra Thapa, Andrya J Durr, Andrew D Taylor, Saira Rizwan, Daud Sharif, Stephen J Valentine, John M Hollander
{"title":"N<sup>6</sup>-methyladenosine (M<sup>6</sup>A) in fetal offspring modifies mitochondrial gene expression following gestational nano-TiO<sub>2</sub> inhalation exposure.","authors":"Amina Kunovac, Quincy A Hathaway, Dharendra Thapa, Andrya J Durr, Andrew D Taylor, Saira Rizwan, Daud Sharif, Stephen J Valentine, John M Hollander","doi":"10.1080/17435390.2023.2293144","DOIUrl":"10.1080/17435390.2023.2293144","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prominent epitranscriptomic modification to RNA in eukaryotes, but it's role in adaptive changes within the gestational environment are poorly understood. We propose that gestational exposure to nano titanium dioxide (TiO<sub>2</sub>) contributes to cardiac m<sup>6</sup>A methylation in fetal offspring and influences mitochondrial gene expression. 10-week-old pregnant female FVB/NJ wild-type mice underwent 6 nonconsecutive days of whole-body inhalation exposure beginning on gestational day (GD) 5. Mice were exposed to filtered room air or nano-TiO<sub>2</sub> with a target aerosol mass concentration of 12 mg/m<sup>3</sup>. At GD 15 mice were humanely killed and cardiac RNA and mitochondrial proteins extracted. Immunoprecipitation with m<sup>6</sup>A antibodies was performed followed by sequencing of immunoprecipitant (m<sup>6</sup>A) and input (mRNA) on the Illumina NextSeq 2000. Protein extraction, preparation, and LC-MS/MS were used for mitochondrial protein quantification. There were no differences in maternal or fetal pup weights, number of pups, or pup heart weights between exposure and control groups. Transcriptomic sequencing revealed 3648 differentially expressed mRNA in nano-TiO<sub>2</sub> exposed mice (<i>Padj</i> ≤ 0.05). Transcripts involved in mitochondrial bioenergetics were significantly downregulated (83 of 85 genes). 921 transcripts revealed significant m<sup>6</sup>A methylation sites (<i>Padj</i> ≤ 0.10). 311 of the 921 mRNA were identified to have both 1) significantly altered expression and 2) differentially methylated sites. Mitochondrial proteomics revealed decreased expression of ATP Synthase subunits in the exposed group (<i>P</i> ≤ 0.05). The lack of m<sup>6</sup>A modifications to mitochondrial transcripts suggests a mechanism for decreased transcript stability and reduced protein expression due to gestational nano-TiO<sub>2</sub> inhalation exposure.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"651-668"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-12-01Epub Date: 2024-01-18DOI: 10.1080/17435390.2023.2297048
James M Antonini, Vamsi Kodali, Terence G Meighan, Walter McKinney, Jared L Cumpston, Howard D Leonard, James B Cumpston, Sherri Friend, Stephen S Leonard, Ronnee Andrews, Patti C Zeidler-Erdely, Aaron Erdely, Eun Gyung Lee, Aliakbar A Afshari
{"title":"Lung toxicity, deposition, and clearance of thermal spray coating particles with different metal profiles after inhalation in rats.","authors":"James M Antonini, Vamsi Kodali, Terence G Meighan, Walter McKinney, Jared L Cumpston, Howard D Leonard, James B Cumpston, Sherri Friend, Stephen S Leonard, Ronnee Andrews, Patti C Zeidler-Erdely, Aaron Erdely, Eun Gyung Lee, Aliakbar A Afshari","doi":"10.1080/17435390.2023.2297048","DOIUrl":"10.1080/17435390.2023.2297048","url":null,"abstract":"<p><p>Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m<sup>3</sup> × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310-378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m<sup>3</sup> × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"669-686"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-08-01Epub Date: 2023-12-01DOI: 10.1080/17435390.2023.2268163
Irini Furxhi, Michal Kalapus, Anna Costa, Tomasz Puzyn
{"title":"Artificial augmented dataset for the enhancement of nano-QSARs models. A methodology based on topological projections.","authors":"Irini Furxhi, Michal Kalapus, Anna Costa, Tomasz Puzyn","doi":"10.1080/17435390.2023.2268163","DOIUrl":"10.1080/17435390.2023.2268163","url":null,"abstract":"<p><p>Nanoinformatics demands accurate predictive models to assess the potential hazards of nanomaterials (NMs). However, limited data availability and the diverse nature of NMs physicochemical properties and their interaction with biological media, hinder the development of robust nano-Quantitative Structure-Activity Relationship (QSAR) models. This article proposes an approach that combines artificially data generation techniques and topological projections to address the challenges of insufficient dataset sizes and their limited representativeness of the chemical space. By leveraging the rich information embedded in the topological features, this methodology enhances the representation of the chemical space, enabling a more an exploration of the structure-activity relationships. We demonstrate the efficacy of our approach through extensive experiments, employing various machine learning regression algorithms to validate the methodology. Finally, we compare two different resampling approaches based on different modeling scenarios. The results showcase a significant improved predictive performance of QSAR models demonstrating a promising strategy to overcome the limitations of small datasets in the field of nanoinformatics. The proposed approach offers noteworthy potential for advancing nanoinformatics research within the nanosafety domain by enabling the development of more accurate predictive models for assessing the potential hazards associated with NMs.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"529-544"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of <i>in vivo</i> assays.","authors":"Nana Sun, Xiaopeng Zhang, Chunlai Liang, Haibo Liu, Yuan Zhi, Jin Fang, Huiling Wang, Zhou Yu, Xudong Jia","doi":"10.1080/17435390.2023.2265467","DOIUrl":"10.1080/17435390.2023.2265467","url":null,"abstract":"Abstract As one representative of nanometal oxides, titanium dioxide nanoparticles (TiO2-NPs) have been widely used, particularly in the food industry. The genotoxicity of TiO2-NPs has attracted great attention over the years. This study was undertaken to investigate the chromosome and DNA damage effects of TiO2-NPs (0, 50, 150, and 500 mg/kg BW) using rodent models. After a comprehensive characterization, we conducted a standard battery of in vivo genotoxicity tests, including the chromosomal aberration test (CA), micronucleus (MN) test, and the comet test. The results of all these tests were negative. There were no structural or numerical chromosomal abnormalities in mice bone marrow cells, no increase in the frequency of micronucleated polychromatic erythrocytes in mice bone marrow cells, and no elevation in % tail DNA in rat hepatocytes. This indicated that TiO2-NPs did not cause chromosomal damage or have a direct impact on DNA. These findings suggested that TiO2-NPs did not exhibit genotoxicity and provided valuable data for risk assessment purposes.","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"497-510"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-08-01Epub Date: 2023-12-01DOI: 10.1080/17435390.2023.2265481
Fátima Brandão, Carla Costa, Maria João Bessa, Vanessa Valdiglesias, Bryan Hellack, Andrea Haase, Sónia Fraga, João Paulo Teixeira
{"title":"Multiparametric <i>in vitro</i> genotoxicity assessment of different variants of amorphous silica nanomaterials in rat alveolar epithelial cells.","authors":"Fátima Brandão, Carla Costa, Maria João Bessa, Vanessa Valdiglesias, Bryan Hellack, Andrea Haase, Sónia Fraga, João Paulo Teixeira","doi":"10.1080/17435390.2023.2265481","DOIUrl":"10.1080/17435390.2023.2265481","url":null,"abstract":"<p><p>The hazard posed to human health by inhaled amorphous silica nanomaterials (aSiO<sub>2</sub> NM) remains uncertain. Herein, we assessed the cyto- and genotoxicity of aSiO<sub>2</sub> NM variants covering different sizes (7, 15, and 40 nm) and surface modifications (unmodified, phosphonate-, amino- and trimethylsilyl-modified) on rat alveolar epithelial (RLE-6TN) cells. Cytotoxicity was evaluated at 24 h after exposure to the aSiO<sub>2</sub> NM variants by the lactate dehydrogenase (LDH) release and WST-1 reduction assays, while genotoxicity was assessed using different endpoints: DNA damage (single- and double-strand breaks [SSB and DSB]) by the comet assay for all aSiO<sub>2</sub> NM variants; cell cycle progression and γ-H2AX levels (DSB) by flow cytometry for those variants that presented higher cytotoxic and DNA damaging potential. The variants with higher surface area demonstrated a higher cytotoxic potential (SiO<sub>2</sub>_7, SiO<sub>2</sub>_15_Unmod, SiO<sub>2</sub>_15_Amino, and SiO<sub>2</sub>_15_Phospho). SiO<sub>2</sub>_40 was the only variant that induced significant DNA damage on RLE-6TN cells. On the other hand, all tested variants (SiO<sub>2</sub>_7, SiO<sub>2</sub>_15_Unmod, SiO<sub>2</sub>_15_Amino, and SiO<sub>2</sub>_40) significantly increased total γ-H2AX levels. At high concentrations (28 µg/cm<sup>2</sup>), a decrease in G<sub>0</sub>/G<sub>1</sub> subpopulation was accompanied by a significant increase in S and G<sub>2</sub>/M sub-populations after exposure to all tested materials except for SiO<sub>2</sub>_40 which did not affect cell cycle progression. Based on the obtained data, the tested variants can be ranked for its genotoxic DNA damage potential as follows: SiO<sub>2</sub>_7 = SiO<sub>2</sub>_40 = SiO<sub>2</sub>_15_Unmod > SiO<sub>2</sub>_15_Amino. Our study supports the usefulness of multiparametric approaches to improve the understanding on NM mechanisms of action and hazard prediction.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"511-528"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49679862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01Epub Date: 2023-09-09DOI: 10.1080/17435390.2023.2255269
Rendong He, Xuefeng Ding, Tingjun Zhang, Linqiang Mei, Shuang Zhu, Chengyan Wang, You Liao, Dongmei Wang, Hao Wang, Junsong Guo, Xiaolan Guo, Yan Xing, Zhanjun Gu, Houxiang Hu
{"title":"Study on myocardial toxicity induced by lead halide perovskites nanoparticles.","authors":"Rendong He, Xuefeng Ding, Tingjun Zhang, Linqiang Mei, Shuang Zhu, Chengyan Wang, You Liao, Dongmei Wang, Hao Wang, Junsong Guo, Xiaolan Guo, Yan Xing, Zhanjun Gu, Houxiang Hu","doi":"10.1080/17435390.2023.2255269","DOIUrl":"10.1080/17435390.2023.2255269","url":null,"abstract":"<p><p>Lead halide perovskites (LHPs) are outstanding candidates for next-generation optoelectronic materials, with considerable prospects of use and commercial value. However, knowledge about their toxicity is scarce, which may limit their commercialization. Here, for the first time, we studied the cardiotoxicity and molecular mechanisms of representative CsPbBr<sub>3</sub> nanoparticles in LHPs. After their intranasal administration to Institute of Cancer Research (ICR) mice, using advanced synchrotron radiation, mass spectrometry, and ultrasound imaging, we revealed that CsPbBr<sub>3</sub> nanoparticles can severely affect cardiac systolic function by accumulating in the myocardial tissue. RNA sequencing and Western blotting demonstrated that CsPbBr<sub>3</sub> nanoparticles induced excessive oxidative stress in cardiomyocytes, thereby provoking endoplasmic reticulum stress, disturbing calcium homeostasis, and ultimately leading to apoptosis. Our findings highlight the cardiotoxic effects of LHPs and provide crucial toxicological data for the product.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"449-470"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01Epub Date: 2023-10-17DOI: 10.1080/17435390.2023.2252921
Qinqin Sun, Jia Yao, Zhijun Zhang, Juan Li, Xue Zhang, Hui Wang, Xufang Du, Min Li, Ying Zhao
{"title":"Facile fabrication of biocompatible injectable blended polymeric hydrogel with bioactive nanoformulation to improving cardiac tissue regeneration efficiency after myocardial infarction for nursing care potential applications.","authors":"Qinqin Sun, Jia Yao, Zhijun Zhang, Juan Li, Xue Zhang, Hui Wang, Xufang Du, Min Li, Ying Zhao","doi":"10.1080/17435390.2023.2252921","DOIUrl":"10.1080/17435390.2023.2252921","url":null,"abstract":"<p><p>Recent years, cardiac vascular disease has arisen owing to acute myocardial infarction (MI) and heart failure leading to death worldwide. Various treatments are available for MI in modern medicine such as implantation of devices, pharmaceutical therapy, and transplantation of organs, nonetheless, it has many complications in finding an organ donor, devices for stenosis, high intrusiveness and long-time hospitalization. To overcome these problems, we have designed and developed a novel hydrogel material with a combination of Se NPs loaded poly(ethylene glycol)/tannic acid (PEG/TA) hydrogel for the treatment of acute MI repair. Herein, Se NPs were characterized by effective analytical and spectroscopic techniques. <i>In vitro</i> cell compatibility and anti-oxidant analyses were examined on human cardiomyocytes in different concentrations of Se NPs and appropriate Se NPs loaded hydrogel samples to demonstrate its greater suitability for <i>in vivo</i> cardiac applications. <i>In vivo</i> investigations of MI mice models injected with Se hydrogels established that LV wall thickness was conserved significantly from the value of 235.6 µm to 390 µm. In addition, the relative scar thickness (33.6%) and infarct size (17.1%) of the MI model were enormously reduced after injection of Se hydrogel when compared to the Se NPs and control (MI) sample, respectively, which confirmed that Se introduced hydrogel have greatly influenced on the restoration of the infarcted heart. Based on the investigated results of the nanoformulation samples, it could be a promising material for future generations treatment of acute myocardial infarction and cardiac repair applications.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"432-448"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10303014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}