Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells

Kenzaoui, Blanka Halamoda; Bernasconi, Catherine Chapuis; Guney-Ayra, Seher; Juillerat‐Jeanneret, Lucienne

doi:10.1042/bj20111252

Cited by 194 publications

(84 citation statements)

References 43 publications

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“…The TEM images of the formed Ti aggregates in the present study were very similar to the solubilized TiO 2 nanoparticles in human serum, which were shown by Soto‐Alvaredo et al61 Uptake of phagocytized TiO 2 in endothelial cells62 and osteoblasts63 appear similar to our present findings in vitro and in human peri‐implantitis tissue. We have shown in this study that phagocytized Ti aggregates could be found in human macrophages in vitro as well in peri‐implantitis tissue.…”

Section: Discussionsupporting

confidence: 91%

Effect of cobalt ions on the interaction between macrophages and titanium

Pettersson

Thorén

et al. 2018

J Biomedical Materials Res

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Inflammation and bone reduction around dental implants are described as peri‐implantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL‐1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro‐inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP‐1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL‐1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy and electron microscopy. Co at a concentration of 100 µM neutralized the IL‐1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti‐induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti‐induced activation and release of active IL‐1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal‐protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localisation after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri‐implant tissue. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2518–2530, 2018.

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Section: Discussionsupporting

confidence: 91%

Effect of cobalt ions on the interaction between macrophages and titanium

Pettersson

Thorén

et al. 2018

J Biomedical Materials Res

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“…Among the phenotypic changes reported to be associated with the biomedical application of NPs are cellular stress responses (i.e. redox imbalance, oxidative stress), DNA damage, and altered gene expression (8,9). Which of these phenotypes can be considered a direct consequence of cellular NP association or uptake and the underlying molecular mechanisms have remained in many cases unknown.…”

Section: Nanoparticles (Nps)mentioning

confidence: 99%

Lysosomal Dysfunction Caused by Cellular Accumulation of Silica Nanoparticles

Schütz

López-Hernández

Gao

et al. 2016

Journal of Biological Chemistry

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Nanoparticles (NPs) are widely used as components of drugs or cosmetics and hold great promise for biomedicine, yet their effects on cell physiology remain poorly understood. Here we demonstrate that clathrin-independent dynamin 2-mediated caveolar uptake of surface-functionalized silica nanoparticles (SiNPs) impairs cell viability due to lysosomal dysfunction. We show that internalized SiNPs accumulate in lysosomes resulting in inhibition of autophagy-mediated protein turnover and impaired degradation of internalized epidermal growth factor, whereas endosomal recycling proceeds unperturbed. This phenotype is caused by perturbed delivery of cargo via autophagosomes and late endosomes to SiNP-filled cathepsin B/L-containing lysosomes rather than elevated lysosomal pH or altered mTOR activity. Given the importance of autophagy and lysosomal protein degradation for cellular proteostasis and clearance of aggregated proteins, these results raise the question of beneficial use of NPs in biomedicine and beyond. Nanoparticles (NPs)2 are widely used as components of drugs or cosmetics and hold great promise as tools in biomedicine to improve the detection and treatment of diseases (1). For example, nanoparticle technology has enabled improvements in cancer treatment, ranging from improved efficacy of drug delivery (2) to enhanced immunogenicity of cancer vaccines (3). Moreover, NPs are used as biosensors and biomarkers (4, 5) or for DNA/drug delivery (6). Hence, it is necessary to understand the mechanisms of interaction of NPs with living cells and tissues to assess the biological consequences associated with their application in biomedicine (7). At present, the risks associated with the biomedical application of NPs at the cellular and organismic levels remain incompletely understood (1). Among the phenotypic changes reported to be associated with the biomedical application of NPs are cellular stress responses (i.e. redox imbalance, oxidative stress), DNA damage, and altered gene expression (8,9). Which of these phenotypes can be considered a direct consequence of cellular NP association or uptake and the underlying molecular mechanisms have remained in many cases unknown.Upon cellular application, NPs initially interact with the plasma membrane, often followed by their internalization into the cell interior (10 -12) via clathrin-dependent as well as clathrin-independent endocytosis routes (i.e. via caveolae), which may require the membrane-severing GTPase dynamin (13,14). Due to the questionable specificity of many commonly used pharmacological tools toward these pathways (15) the precise mechanisms of cellular uptake of NPs often have remained elusive. After cell entry NPs are delivered to the endolysosomal system (16), where they may accumulate. Lysosomes play essential roles in cell physiology ranging from the degradation of malfunctional or aggregated proteins (e.g. via autophagy) or lipids to nutrient signaling and cellular growth control (17). For example, internalized growth factors such as EGF are sorted to la...

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“…64,65 Due to the high refractive index, the elastically scattered light from a ND particle is estimated to be 300-fold brighter than a same-sized cell organelle. 65 In addition to increased light scattering, there can be an increased activation of lysosomes for trapping the internalized ND particles, 66 which also contributes toward side scattering. 67 While there is a change in the side scattering, the FS (indicative of the size of the cell) remained unchanged before and after the treatment ( Figure 4B), suggesting that the NDs are internalized into the cells and not adhered to the surface.…”

Section: Flow Cytometrymentioning

confidence: 99%

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Alwani¹,

Kaur²,

Michel³

et al. 2016

IJN

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Purpose Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Results Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization of lys-NDs was confirmed by various techniques such as confocal microscopy, soft X-ray spectroscopy, and flow cytometry. Conclusion This study establishes that dispersion of lys-NDs in aqueous medium maintains long-term stability and also provides evidence that lysine functionalization enables NDs to interact effectively with the biological system to be used for RNAi therapeutics.

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Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells

Cited by 194 publications

References 43 publications

Effect of cobalt ions on the interaction between macrophages and titanium

Effect of cobalt ions on the interaction between macrophages and titanium

Lysosomal Dysfunction Caused by Cellular Accumulation of Silica Nanoparticles

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

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