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15 pages, 3159 KiB

Open AccessEditor’s ChoiceArticle

High-Dose Exposure to Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells

by Thanpisit Lomphithak, Selin Helvacioglu, Ilaria Armenia, Sandeep Keshavan, Jesús G. Ovejero, Giovanni Baldi, Costanza Ravagli, Valeria Grazú and Bengt Fadeel

Nanomaterials 2023, 13(11), 1719; https://doi.org/10.3390/nano13111719 - 24 May 2023

Cited by 9 | Viewed by 2501

Abstract

Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide [...] Read more.

Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe₂O₃ and Fe₂O₃@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe₃O₄-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 μg/mL. However, when the cells were exposed to higher concentrations (200–400 μg/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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19 pages, 9266 KiB

Open AccessArticle

Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents

by Martina B. Violatto, Giovanni Sitia, Laura Talamini, Annalisa Morelli, Ngoc Lan Tran, Qian Zhang, Atif Masood, Beatriz Pelaz, Indranath Chakraborty, Daxiang Cui, Wolfgang J. Parak, Mario Salmona, Neus G. Bastús, Victor Puntes and Paolo Bigini

Nanomaterials 2023, 13(7), 1174; https://doi.org/10.3390/nano13071174 - 25 Mar 2023

Cited by 2 | Viewed by 1941

Abstract

Titanium dioxide nanoparticles (TiO₂ NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets [...] Read more.

Titanium dioxide nanoparticles (TiO₂ NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO₂ NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO₂ NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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15 pages, 1485 KiB

Open AccessArticle

Genotoxicity and Toxicity Assessment of a Formulation Containing Silver Nanoparticles and Kaolin: An In Vivo Integrative Approach

by Adriana Rodriguez-Garraus, María Alonso-Jauregui, Ana-Gloria Gil, Iñigo Navarro-Blasco, Adela López de Cerain and Amaya Azqueta

Nanomaterials 2023, 13(1), 3; https://doi.org/10.3390/nano13010003 - 20 Dec 2022

Cited by 6 | Viewed by 1791

Abstract

A new material composed of a kaolin base with silver nanoparticles (AgNPs) attached to its surface was developed, as an alternative to antibiotics used as supplements in animal feed. As part of its safety assessment, an in vivo geno-toxicological evaluation of this material [...] Read more.

A new material composed of a kaolin base with silver nanoparticles (AgNPs) attached to its surface was developed, as an alternative to antibiotics used as supplements in animal feed. As part of its safety assessment, an in vivo geno-toxicological evaluation of this material was conducted in rats. First, a preliminary dose finding study was carried out to decide the doses to be tested in the main study: 50, 300 and 2000 mg/kg b.w. For the main study, a combined strategy composed of the MN test (TG 474) and the comet assay (TG 489), integrated in a repeated dose 28-day oral toxicity study (TG 407), was performed. A No Observed Adverse Effect Level (NOAEL) of 2000 mg of the silver-kaolin formulation/kg b.w. by oral route, for 28 days, was determined. The silver-kaolin formulation did not induce micronuclei in bone marrow, or DNA strand breaks (SBs) or alkali labile sites (ALS) in liver, spleen, kidney or duodenum at any dose. The modified Fpg comet assay did not reveal oxidized bases in the same tissues at the dose of 2000 mg/kg b.w. Silver was quantified by ICP-MS in all the target organs, confirming the negative results obtained under these conditions. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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13 pages, 7461 KiB

Open AccessArticle

In Situ Facile Synthesis of Low-Cost Biogenic Eggshell-Derived Nanohydroxyapatite/Chitosan Biocomposites for Orthopedic Implant Applications

by Sankar Sekar and Sejoon Lee

Nanomaterials 2022, 12(23), 4302; https://doi.org/10.3390/nano12234302 - 4 Dec 2022

Cited by 2 | Viewed by 1710

Abstract

In situ facile synthesis and the characterization of nanohydroxyapatite/chitosan (nHAP/CS) biocomposites were investigated for examining their potential applications in orthopedic implant technology. Firstly, the bare nHAP, europium-doped hydroxyapatite (Eu-nHAP), yttrium-doped hydroxyapatite (Y-nHAP), and Eu- and Y-codoped hydroxyapatite (Eu,Y-nHAP) nanoparticles were synthesized by the [...] Read more.

In situ facile synthesis and the characterization of nanohydroxyapatite/chitosan (nHAP/CS) biocomposites were investigated for examining their potential applications in orthopedic implant technology. Firstly, the bare nHAP, europium-doped hydroxyapatite (Eu-nHAP), yttrium-doped hydroxyapatite (Y-nHAP), and Eu- and Y-codoped hydroxyapatite (Eu,Y-nHAP) nanoparticles were synthesized by the wet precipitation technique using biowaste-eggshell-derived calcium oxide powders. Then, through ultrasonication using the nanohydroxyapatite/chitosan mixtures (molar ratio = 1:2), the nHAP/CS, Eu-nHAP/CS, Y-nHAP/CS, and Eu,Y-nHAP/CS biocomposites were fabricated. Among them, Eu,Y-nHAP/CS showed higher cell viability (94.9%), higher solubility (pH = 7.6 after 21 days), and greater antibacterial activity than those of the other composites. In addition, Eu,Y-nHAP/CS exhibited improved mechanical properties compared with the other composites. For example, the nanoindentation test displayed the Eu,Y-nHAP/CS-coated 316L stainless steel implant to possess a higher Young’s modulus value (9.24 GPa) and greater hardness value (300.71 MPa) than those of the others. The results indicate that the biomass-eggshell-derived Eu,Y-doped nHAP is of good use for orthopedic implant applications. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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17 pages, 2541 KiB

Open AccessArticle

Physico-Chemical Transformation and Toxicity of Multi-Shell InP Quantum Dots under Simulated Sunlight Irradiation, in an Environmentally Realistic Scenario

by Fanny Dussert, Géraldine Sarret, Karl David Wegner, Olivier Proux, Gautier Landrot, Pierre-Henry Jouneau, Peter Reiss and Marie Carrière

Nanomaterials 2022, 12(20), 3703; https://doi.org/10.3390/nano12203703 - 21 Oct 2022

Cited by 8 | Viewed by 2113

Abstract

Quantum dots (QDs) are widely used in optoelectronics, lighting, and photovoltaics leading to their potential release into the environment. The most promising alternative to the highly toxic cadmium selenide (CdSe) QDs are indium phosphide (InP) QDs, which show reduced toxicity and comparable optical [...] Read more.

Quantum dots (QDs) are widely used in optoelectronics, lighting, and photovoltaics leading to their potential release into the environment. The most promising alternative to the highly toxic cadmium selenide (CdSe) QDs are indium phosphide (InP) QDs, which show reduced toxicity and comparable optical and electronic properties. QD degradation leads to the release of toxic metal ions into the environment. Coating the QD core with robust shell(s) composed of another semi-conductor material enhances their properties and protects the QD from degradation. We recently developed double-shelled InP QDs, which proved to be less toxic than single-shell QDs. In the present study, we confirm their reduced cytotoxicity, with an LC50 at 77 nM for pristine gradient shell QDs and >100 nM for pristine thin and thick shell QDs. We also confirm that these three QDs, when exposed to simulated sunlight, show greater cytotoxicity compared to pristine ones, with LC50 ranging from 15 to 23 nM. Using a combination of spectroscopic and microscopic techniques, we characterize the degradation kinetics and transformation products of single- and double-shell QDs, when exposed to solar light at high temperature, simulating environmental conditions. Non-toxic pristine QDs degrade to form toxic In–phosphate, In–carboxylate, Zn–phosphate, and oxidized Se, all of which precipitate as heterogeneous deposits. Comparison of their degradation kinetics highlights that the QDs bearing the thickest ZnS outer shell are, as expected, the most resistant to photodegradation among the three tested QDs, as gradient shell, thin shell, and thick shell QDs lose their optical properties in less than 15 min, 60 min, and more than 90 min, respectively. They exhibit the highest photoluminescence efficiency, i.e., the best functionality, with a photoluminescence quantum yield in aqueous solution of 24%, as compared to 18% for the gradient shell and thin shell QDs. Therefore, they can be considered as safer-by-design QDs. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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20 pages, 4664 KiB

Open AccessArticle

Distinct Uptake Routes Participate in Silver Nanoparticle Engulfment by Earthworm and Human Immune Cells

by Bohdana Kokhanyuk, Viola Bagóné Vántus, Balázs Radnai, Eszter Vámos, Gyula Kajner, Gábor Galbács, Elek Telek, Mária Mészáros, Mária A. Deli, Péter Németh and Péter Engelmann

Nanomaterials 2022, 12(16), 2818; https://doi.org/10.3390/nano12162818 - 17 Aug 2022

Cited by 2 | Viewed by 2345

Abstract

The consequences of engineered silver nanoparticle (AgNP) exposure and cellular interaction with the immune system are poorly understood. The immunocytes of the Eisenia andrei earthworm are frequently applied in ecotoxicological studies and possess functional similarity to vertebrate macrophages. Hence, we characterized and compared [...] Read more.

The consequences of engineered silver nanoparticle (AgNP) exposure and cellular interaction with the immune system are poorly understood. The immunocytes of the Eisenia andrei earthworm are frequently applied in ecotoxicological studies and possess functional similarity to vertebrate macrophages. Hence, we characterized and compared the endocytosis mechanisms for the uptake of 75 nm AgNPs by earthworm coelomocytes, human THP-1 monocytes, and differentiated THP-1 (macrophage-like) cells. Our results indicate that microtubule-dependent, scavenger–receptor, and PI3K signaling-mediated macropinocytosis are utilized during AgNP engulfment by human THP-1 and differentiated THP-1 cells. However, earthworm coelomocytes employ actin-dependent phagocytosis during AgNPs uptake. In both human and earthworm immunocytes, AgNPs were located in the cytoplasm, within the endo-/lysosomes. We detected that the internalization of AgNPs is TLR/MyD88-dependent, also involving the bactericidal/permeability-increasing protein (BPI) in the case of human immunocytes. The exposure led to decreased mitochondrial respiration in human immunocytes; however, in coelomocytes, it enhanced respiratory parameters. Our findings provide more data about NP trafficking as nano-carriers in the nanomedicine field, as well as contribute to an understanding of the ecotoxicological consequences of nanoparticle exposure. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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12 pages, 3928 KiB

Open AccessArticle

The Dose- and Time-Dependent Cytotoxic Effect of Graphene Nanoplatelets: In Vitro and In Vivo Study

by Hana Bavorova, Tereza Svadlakova, Zdenek Fiala, Rishikaysh Pisal and Jaroslav Mokry

Nanomaterials 2022, 12(12), 1978; https://doi.org/10.3390/nano12121978 - 9 Jun 2022

Cited by 2 | Viewed by 1833

Abstract

Graphene-based nanomaterials received attention from scientists due to their unique properties: they are highly conductive, mechanically resistant and elastic. These materials can be used in different sectors of society from electronic energy storage in industry to biomedical applications. This study evaluates the influence [...] Read more.

Graphene-based nanomaterials received attention from scientists due to their unique properties: they are highly conductive, mechanically resistant and elastic. These materials can be used in different sectors of society from electronic energy storage in industry to biomedical applications. This study evaluates the influence of graphene nanoplatelets in vitro and in vivo. The toxicological influence of graphene nanoplatelets (GPs) was analyzed by cytotoxic methods, the change of cell proliferation was assessed in real-time, and the effect of GPs on a living organism was evaluated in an animal model using histopathological examination. We analyzed two types of GP administration: intratracheal and peroral. We found dose- and time-dependent cytotoxic effects of GPs in vitro; the concentration above 50 μg/mL increased the cytotoxicity significantly. The real-time analysis confirmed these data; the cells exposed to a high concentration of GPs for a longer time period resulted in a decrease in cell index which indicated lower cell viability. Histopathological examination revealed thickened alveolar septa and accumulation of GPs in the endocardium after intratracheal exposure. Peroral administration did not reveal any morphological changes. This study showed the dose- and time-dependent cytotoxic potential of graphene nanoplatelets in in vitro and in vivo models. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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Review

Jump to: Research

22 pages, 1378 KiB

Open AccessEditor’s ChoiceReview

The Effect of Nanomaterials on DNA Methylation: A Review

by Ana Valente, Luís Vieira, Maria João Silva and Célia Ventura

Nanomaterials 2023, 13(12), 1880; https://doi.org/10.3390/nano13121880 - 17 Jun 2023

Cited by 5 | Viewed by 7728

Abstract

DNA methylation is an epigenetic mechanism that involves the addition of a methyl group to a cytosine residue in CpG dinucleotides, which are particularly abundant in gene promoter regions. Several studies have highlighted the role that modifications of DNA methylation may have on [...] Read more.

DNA methylation is an epigenetic mechanism that involves the addition of a methyl group to a cytosine residue in CpG dinucleotides, which are particularly abundant in gene promoter regions. Several studies have highlighted the role that modifications of DNA methylation may have on the adverse health effects caused by exposure to environmental toxicants. One group of xenobiotics that is increasingly present in our daily lives are nanomaterials, whose unique physicochemical properties make them interesting for a large number of industrial and biomedical applications. Their widespread use has raised concerns about human exposure, and several toxicological studies have been performed, although the studies focusing on nanomaterials’ effect on DNA methylation are still limited. The aim of this review is to investigate the possible impact of nanomaterials on DNA methylation. From the 70 studies found eligible for data analysis, the majority were in vitro, with about half using cell models related to the lungs. Among the in vivo studies, several animal models were used, but most were mice models. Only two studies were performed on human exposed populations. Global DNA methylation analyses was the most frequently applied approach. Although no trend towards hypo- or hyper-methylation could be observed, the importance of this epigenetic mechanism in the molecular response to nanomaterials is evident. Furthermore, methylation analysis of target genes and, particularly, the application of comprehensive DNA methylation analysis techniques, such as genome-wide sequencing, allowed identifying differentially methylated genes after nanomaterial exposure and affected molecular pathways, contributing to the understanding of their possible adverse health effects. Full article

(This article belongs to the Special Issue Interaction of Nanomaterials with Biological Systems: In Vitro and In Vivo Studies)

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