Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells

Královec, Karel; Havelek, Radim; Kročová, Eliška; Kučírková, Lucie; Hauschke, Martina; Bartáček, Jan; Palarčík, Jiří; Sedlák, Miloš

doi:10.1016/j.mrgentox.2019.05.015

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…The results of this study have shown that, when treated overnight with MSNs at a concentration of 120 µg/mL, HEK293 cells presented up- or downregulated expression of certain genes and DNA degradation [ 157 ]. Královec and colleagues evaluated the cytotoxic and genotoxic potential of silica-coated iron-oxide nanoparticles (IONPs) in human HK-2 renal proximal tubule epithelial cells and reported severe disruption of the microtubule cytoskeleton structure, which resulted in antiproliferative and cytotoxic effects [ 158 ]. In this study, genotoxic effects were also described after short term exposure to 25 and 100 μg/mL of silica-coated IONPs [ 158 ].…”

Section: Biocompatibility Of Silica-based Materialsmentioning

confidence: 99%

“…Královec and colleagues evaluated the cytotoxic and genotoxic potential of silica-coated iron-oxide nanoparticles (IONPs) in human HK-2 renal proximal tubule epithelial cells and reported severe disruption of the microtubule cytoskeleton structure, which resulted in antiproliferative and cytotoxic effects [ 158 ]. In this study, genotoxic effects were also described after short term exposure to 25 and 100 μg/mL of silica-coated IONPs [ 158 ]. However, different studies have also reported very limited genotoxicity of silica nanoparticles, being this a controversial subject [ 152 , 159 ].…”

Section: Biocompatibility Of Silica-based Materialsmentioning

confidence: 99%

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Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

2020

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Advances in gene therapy have been foreshadowing its potential for the treatment of a vast range of diseases involving genetic malfunctioning. However, its therapeutic efficiency and successful outcome are highly dependent on the development of the ideal gene delivery system. On that matter, silica-based vectors have diverted some attention from viral and other types of non-viral vectors due to their increased safety, easily modifiable structure and surface, high stability, and cost-effectiveness. The versatility of silane chemistry and the combination of silica with other materials, such as polymers, lipids, or inorganic particles, has resulted in the development of carriers with great loading capacities, ability to effectively protect and bind genetic material, targeted delivery, and stimuli-responsive release of cargos. Promising results have been obtained both in vitro and in vivo using these nanosystems as multifunctional platforms in different potential therapeutic areas, such as cancer or brain therapies, sometimes combined with imaging functions. Herein, the current advances in silica-based systems designed for gene therapy are reviewed, including their main properties, fabrication methods, surface modifications, and potential therapeutic applications.

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Section: Biocompatibility Of Silica-based Materialsmentioning

confidence: 99%

Section: Biocompatibility Of Silica-based Materialsmentioning

confidence: 99%

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

2020

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“…The HK-2 is a human immortalized cell line used to predict the nephrotoxicity of various xenobiotics including inorganic nanoparticles, especially on tubular proximal cells [14,23,24]. Its ability to elucidate the renal toxicity mechanisms of xenobiotics is based on the cells' expression of many enzymes and transport proteins that mediate the filtration and reabsorption in the kidneys [23].…”

Section: Discussionmentioning

confidence: 99%

Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells

et al. 2020

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Gold nanoparticles (AuNPs) are highly attractive for biomedical applications. Therefore, several in vitro and in vivo studies have addressed their safety evaluation. Nevertheless, there is a lack of knowledge regarding their potential detrimental effect on human kidney. To evaluate this effect, AuNPs with different sizes (13 nm and 60 nm), shapes (spheres and stars), and coated with 11-mercaptoundecanoic acid (MUA) or with sodium citrate, were synthesized, characterized, and their toxicological effects evaluated 24 h after incubation with a proximal tubular cell line derived from normal human kidney (HK-2). After exposure, viability was assessed by the MTT assay. Changes in lysosomal integrity, mitochondrial membrane potential (ΔΨm), reactive species (ROS/RNS), intracellular glutathione (total GSH), and ATP were also evaluated. Apoptosis was investigated through the evaluation of the activity of caspases 3, 8 and 9. Overall, the tested AuNPs targeted mainly the mitochondria in a concentration-dependent manner. The lysosomal integrity was also affected but to a lower extent. The smaller 13 nm nanospheres (both citrate- and MUA-coated) proved to be the most toxic among all types of AuNPs, increasing ROS production and decreasing mitochondrial membrane potential (p ≤ 0.01). For the MUA-coated 13 nm nanospheres, these effects were associated also to increased levels of total glutathione (p ≤ 0.01) and enhanced ATP production (p ≤ 0.05). Programmed cell death was detected through the activation of both extrinsic and intrinsic pathways (caspase 8 and 9) (p ≤ 0.05). We found that the larger 60 nm AuNPs, both nanospheres and nanostars, are apparently less toxic than their smaller counter parts. Considering the results herein presented, it should be taken into consideration that even if renal clearance of the AuNPs is desirable, since it would prevent accumulation and detrimental effects in other organs, a possible intracellular accumulation of AuNPs in kidneys can induce cell damage and later compromise kidney function.

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“…The present study is mainly devoted to the analysis of biological effects of the final silica‐coated ε‐Fe 2 ‐ x Ga x O 3 nanoparticles on cell models in vitro. The effects of silica‐coated nanoparticles on cells have been demonstrated repeatedly in various cancer cell lines of different tissue origin, immortalized cell lines, human and mouse fibroblasts and human peripheral blood lymphocytes (Guo, Mao, Wang, Yang, & Bai, ; Královec et al, ; Lankoff et al, ; Malvindi et al, ; Yang et al, ). In spite of these numerous reports, only a very limited number of in vitro studies have examined the effect of silica‐coated particles on the cytoskeletal structures and their cellular functions (Královec et al, ).…”

Section: Introductionmentioning

confidence: 97%

“…The effects of silica‐coated nanoparticles on cells have been demonstrated repeatedly in various cancer cell lines of different tissue origin, immortalized cell lines, human and mouse fibroblasts and human peripheral blood lymphocytes (Guo, Mao, Wang, Yang, & Bai, ; Královec et al, ; Lankoff et al, ; Malvindi et al, ; Yang et al, ). In spite of these numerous reports, only a very limited number of in vitro studies have examined the effect of silica‐coated particles on the cytoskeletal structures and their cellular functions (Královec et al, ). However, the previous studies have reported that various nanoparticles, including titania nanoparticles (Ibrahim, Schoelermann, Mustafa, & Cimpan, ), citric acid and dextran/carboxy dextran‐coated iron oxide nanoparticles (Soenen, Himmelreich, Nuytten, & De Cuyper, ; Soenen, Nuytten, De Meyer, De Smedt, & De Cuyper, ; Wu, Tan, Mao, & Zhang, ), magnetoliposomes, and citrate‐coated very small iron oxide particles (Soenen et al, , ) can affect actin and microtubule cytoskeleton as well as focal adhesion proteins and subsequently the adhesion to the extracellular matrix.…”

Section: Introductionmentioning

confidence: 97%

Magnetic nanoparticles of Ga‐substituted ε‐Fe₂O₃ for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica‐coated particles on cytoskeletal networks

Královec

Havelek

Koutová

et al. 2020

J Biomedical Materials Res

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Magnetic nanoparticles of ε-Fe 1.76 Ga 0.24 O 3 with the volume-weighted mean size of 17 nm were prepared by thermal treatment of a mesoporous silica template impregnated with metal nitrates and were coated with silica shell of four different thicknesses in the range 6-24 nm. The bare particles exhibited higher magnetization than the undoped compound, 22.4 Am 2 kg −1 at 300 K, and were characterized by blocked state with the coercivity of 1.2 T at 300 K, being thus the very opposite of superparamagnetic iron oxides. The relaxometric study of the silica-coated samples at 0.47 T revealed promising properties for MRI, specifically, transverse relaxivity of 89-168 s −1 mmol(f.u.) −1 L depending on the shell thickness was observed. We investigated the effects of the silica-coated nanoparticles on human A549 and MCF-7 cells. Cell viability, proliferation, cell cycle distribution, and the arrangement of actin cytoskeleton were assessed, as well as formation and maturation of focal adhesions.Our study revealed that high concentrations of silica-coated particles with larger shell thicknesses of 16-24 nm interfere with the actin cytoskeletal networks, inducing thus morphological changes. Consequently, the focal adhesion areas were significantly decreased, resulting in impaired cell adhesion. K E Y W O R D S cytoskeleton, cytotoxicity, epsilon polymorph, Ga-doped iron(III) oxide, transverse relaxivity How to cite this article: Královec K, Havelek R, Koutová D, et al. Magnetic nanoparticles of Ga-substituted ε-Fe 2 O 3 for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica-coated particles on cytoskeletal networks.

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Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells

Abstract: 2019). Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis.

Cited by 9 publications

References 49 publications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells

Magnetic nanoparticles of Ga‐substituted ε‐Fe₂O₃ for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica‐coated particles on cytoskeletal networks

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Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells

Abstract: 2019). Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis.

Cited by 9 publications

References 49 publications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells

Magnetic nanoparticles of Ga‐substituted ε‐Fe2O3 for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica‐coated particles on cytoskeletal networks

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Product

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Magnetic nanoparticles of Ga‐substituted ε‐Fe₂O₃ for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica‐coated particles on cytoskeletal networks