Percorrer por autor "Touzani, Assia"
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- Biocompatibility evaluation of CeO2 nanoparticles to be employed as nanodrugs in brain cancer nanomedicinePublication . Fernández-Bertólez, Natália; Touzani, Assia; Martínez, L.; Reis, Ana Teresa; Fraga, Sónia; Teixeira, João Paulo; Costa, Carla; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaCerium dioxide nanoparticles (CeO2NP) have recently gained attention for their unique structure-dependent properties, antioxidant enzyme-like behaviour, ROS scavenging activity and great potential for biomedical applications. In addition to their antioxidant and anti-inflammatory activity, CeO2NP are also known to exhibit anticancer potential, providing an attractive opportunity for use in cancer therapy, as a pharmacological agent and/or in drug/gene delivery systems [1]. Therefore, the main objective of this STSM was to evaluate the cytotoxic and genotoxic effects on human glioblastoma A172 cells exposed for 3, 24 and 48h to CeO2NP (1- 100µg/ml), to verify their safety to be used as possible nanomedicines for brain cancer treatment, specifically glioblastoma [2]. In addition, cell-specific differences in nanoceria effect were evaluated by comparing the results obtained with those observed in human neuronal SH-SY5Y cells exposed under the same experimental conditions. After carrying out the physicochemical characterization and analysing the cellular uptake of the CeO2NP, potential alterations in cell viability (MTT assay) and induction of DNA double-strand breaks (γH2AX assay) caused by the exposure were determined. The possible NP interference with assay methodologies was previously addressed and eliminated when necessary. Results obtained showed that, although there was a significant dose- and time-dependent internalization of NP by both cell types, nanoceria induced scarce cytotoxicity or genotoxicity in both cell lines, being restricted to the highest doses and longer exposure time tested. In general, data obtained suggest a high biocompatibility of CeO2NP under the tested conditions, except for glioblastoma cells exposed for 48h from 25 to 100µg/ml. These results provide a better understanding of the CeO2NP interaction with nervous system cells and their possible adverse effects. However, further studies are necessary to delve into the differential behaviour of these NP depending on the nervous cell type tested.
- Biocompatibility testing and antioxidant properties of cerium dioxide nanoparticles in human nervous system cellsPublication . Fernández-Bertólez, Natalia; Touzani, Assia; Ramos-Pan, Lucía; Reis, Ana Teresa; Teixeira, João Paulo; Laffon, Blanca; Valdiglesias, VanessaCerium dioxide nanoparticles (CeO NP), or nanoceria, are versatile materials with interesting properties for industry and medicine fields, particularly redox properties and catalytic activity. Because of their distinctive features, they have gained high attention in biomedical and pharmacological research to be employed in drug delivery, tissue regeneration, radioprotection, or diagnostic imaging. However, previous works reported that nanoceria may also induce reactive oxygen species (ROS) under certain conditions, leading to cellular stress, cellular damage, or cell death. In this study, the effects of CeO NP on cell viability and morphology as well as their influence on oxidative stress (both oxidant and ROS scavenging capacities) were investigated in nervous system cells (SH-SY5Y neuronal and A172 glial cells) treated with a wide range of CeO NP concentrations (1-100 µg/mL) for several treatment times. Results obtained showed that, despite being stable in time and effectively internalized by both cell types, CeO NP did not produce significant decrease in viability, evaluated by MTT assay, morphological alterations, or intrinsic cell-free ROS, but they generated cellular ROS limited to longer exposure periods. Furthermore, CeO NP demonstrated a certain intrinsic ability to scavenge ROS generated by HO in both tested cell types, more pronounced in neuronal cells. These results confirm the good biocompatibility of nanoceria on human nervous system cells and support further exploring their potential use in biomedicine field, particularly for those therapeutic and diagnostic applications related to the nervous system.
- Effects of Zinc Oxide Nanoparticle Exposure on Human Glial Cells and Zebrafish EmbryosPublication . Valdiglesias, Vanessa; Alba-González, Anabel; Fernández-Bertólez, Natalia; Touzani, Assia; Ramos-Pan, Lucía; Reis, Ana Teresa; Moreda-Piñeiro, Jorge; Yáñez, Julián; Laffon, Blanca; Folgueira, MónicaZinc oxide nanoparticles (ZnO NPs) are among the most widely used nanomaterials. They have multiple applications in cosmetics, textiles, paints, electronics and, recently, also in biomedicine. This extensive use of ZnO NPs notably increases the probability that both humans and wildlife are subjected to undesirable effects. Despite being among the most studied NPs from a toxicological point of view, much remains unknown about their ecotoxicological effects or how they may affect specific cell types, such as cells of the central nervous system. The main objective of this work was to investigate the effects of ZnO NPs on human glial cells and zebrafish embryo development and to explore the role of the released Zn2+ ions in these effects. The effects on cell viability on human A172 glial cells were assessed with an MTT assay and morphological analysis. The potential acute and developmental toxicity was assessed employing zebrafish (Danio rerio) embryos. To determine the role of Zn2+ ions in the in vitro and in vivo observed effects, we measured their release from ZnO NPs with flame atomic absorption spectrometry. Then, cells and zebrafish embryos were treated with a water-soluble salt (zinc sulfate) at concentrations that equal the number of Zn2+ ions released by the tested concentrations of ZnO NPs. Exposure to ZnO NPs induced morphological alterations and a significant decrease in cell viability depending on the concentration and duration of treatment, even after removing the overestimation due to NP interference. Although there were no signs of acute toxicity in zebrafish embryos, a decrease in hatching was detected after exposure to the highest ZnO NP concentrations tested. The ability of ZnO NPs to release Zn2+ ions into the medium in a concentration-dependent manner was confirmed. Zn2+ ions did not seem entirely responsible for the effects observed in the glial cells, but they were likely responsible for the decrease in zebrafish hatching rate. The results obtained in this work contribute to the knowledge of the toxicological potential of ZnO NPs.
- Impact of gold nanoparticle exposure on genetic materialPublication . Ramos-Pan, Lucía; Touzani, Assia; Fernández-Bertólez, Natalia; Fraga, Sónia; Laffon, Blanca; Valdiglesias, VanessaMetal nanoparticles, with gold nanoparticles (AuNP) at the forefront, have gained immense attention due to their unique properties. At the nanoscale, gold exhibits remarkable physical, chemical, optical, and electronic features, making it ideal for a plethora of applications, including bioimaging, sensing, diagnostics, and drug delivery. Despite their promising utility, concerns have arisen regarding the potential adverse effects of AuNP on human health. Research has indicated that these nanoparticles can accumulate in vital organs and interact with proteins and cellular structures, potentially leading to diverse toxicological manifestations. The precise understanding of these nano-bio interactions is further complicated by the varied physicochemical properties of AuNP that influence their biological effects. This review aims to consolidate the current knowledge on the genotoxic effects of AuNP, shedding light on the underlying mechanisms and factors affecting their toxicity. The search was conducted in PubMed and Web of Science databases. Eventually, 32 studies focusing on the genotoxic effects of AuNP were included in the review. In vitro and in vivo findings revealed that AuNP can induce primary DNA damage, oxidative DNA damage, chromosomal damage, alterations in gene expression, and effects on epigenetic regulation. These effects were found to be influenced by various factors, including nanoparticle size, shape, and surface coating. However, the existing literature also highlights the challenges associated with assessing the genotoxicity of nanomaterials (NM), emphasizing the need for standardized and adapted testing protocols. The interference of nanoparticles with conventional toxicity assays may lead to unreliable results; thus, specific methodologies tailored for NM evaluation must be implemented. In conclusion, while AuNP hold tremendous potential for innovative applications, their safety profile remains a critical concern. Continued research is imperative to elucidate the mechanisms of AuNP induced genotoxicity and develop robust testing protocols, ensuring their safe and effective use in diverse applications.
- In vitro and in vivo assessment of nanoceria biocompatibility for their safe use in nervous system applicationsPublication . Fernández-Bertólez, Natalia; Martínez, Luisa; Ramos-Pan, Lucía; Touzani, Assia; Costa, Carla; Laffon, Blanca; Valdiglesias, VanessaNanoceria, or cerium dioxide nanoparticles (CeO NP), are increasingly employed in a number of industrial and commercial applications. Hence, the environmental presence of these nanoparticles is growing progressively, enhancing the global concern on their potential health effects. Recent studies suggest that nanoceria may also have promising biomedical applications particularly in neurodegenerative and brain-related pathologies, but studies addressing their toxicity, and specifically on the nervous system, are still scarce, and their potential adverse effects and action mechanism are not totally understood yet. The objective of this work was to assess the biological behaviour of CeO NP in vitro in human nervous systems cells, and in vivo in Drosophila melanogaster to characterize their safety for exposed individuals and verify their suitability to be further employed in diagnosis and treatment of nervous system disorders. Cell cycle alterations, late apoptosis rate and DNA damage (comet and γH2AX assays), were determined in neuronal SH-SY5Y and glial A172 cells treated with nanoceria. Moreover, the survival rate, morphological changes and behavioural alterations were analysed in D. melanogaster individuals chronically exposed to CeO NP. The results obtained from the in vitro assessment showed that the nanoceria generally presented a good biocompatibility with scarce cyto- or genotoxic effects, essentially depending the exposure time and cell type, and being restricted to the longer exposure periods. Nevertheless, decrease in adult size and alterations observed in the larval crawling in the in vivo assays highlight the need of further investigations before establishing clinical uses of nanoceria.
- Neuron and Glial Cells Exposed to Cerium Dioxide Nanoparticles: Results from MTT and γH2AX AssaysPublication . Fernández-Bertólez, Natalia; Touzani, Assia; Martínez, Luisa; Méndez, Josefina; Reis, Ana Teresa; Costa, Carla; Fraga, Sonia; Teixeira, João Paulo; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaCerium dioxide nanoparticles (CeO2NP) show antioxidant enzyme-like properties and reactive oxygen species (ROS) scavenging activity, making them a promising material for potential therapeutic applications in neurodegenerative diseases. The objective of this work was to assess the biological behavior of CeO2NP in human SH-SY5Y neuronal and A172 glial cells by means of the MTT assay and the γH2AX assay. Despite the significant dose- and time-dependent NP internalization by both cell lines, nanoceria generally presented scarce cytotoxicity or genotoxicity, essentially restricted to the highest NP doses and longest exposure times. In conclusion, a high biocompatibility of CeO2NP was observed under the conditions tested.
- Systematic review on toxicological effects of platinum nanoparticles: towards their use as safe biomedical toolsPublication . Touzani, Assia; Ramos-Pan, Lucía; Fraga, Sónia; Fernández-Bertólez, Natalia; Laffon, Blanca; Valdiglesias, VanessaPlatinum nanoparticles (PtNP) have received considerable attention in the nanomedicine field due to their magnetic, catalytic, and optical properties. However, the potential toxicity of PtNP has not been properly evaluated yet, and current information on the possible risks related to their use is still limited. On this basis, the main objective of this systematic review was to gather available data on PtNP biological behaviour and potential harmful effects, as well as to highlight the gaps of knowledge that need to be filled in to progress in their use in clinical practice. A total of 441 studies were obtained and reviewed from the initial search; 108 fulfilled the selection criteria and were included in the revision. Mainly in vitro but also in vivo studies were reported using a variety of biological systems and animal models, with no data from human epidemiological studies published so far. All these studies were extensively evaluated to provide useful information on the PtNP biocompatibility and their potential to be employed for medical purposes. In particular, information on the physicochemical features of the PtNP influencing their biological behaviour, methods employed for toxicity evaluation, biological systems used, and outcomes addressed were analysed and discussed. In general, the results obtained showed a good biocompatibility of these NP, although some of them detected significant toxicity highly dependent of size, concentration/dose, coating, or exposed biological system. Furthermore, anticancer or protective effects were also described for PtNP in several revised studies. These findings encourage to continue exploring the benefits of PtNP for clinical practice.