Silica nanoparticle uptake induces survival mechanism in A549 cells by the activation of autophagy but not apoptosis

Nowak, Jakub Stanislaw; Méhn, Dóra; Nativo, Paola; García, César Pascual; Gioria, Sabrina; Ojea-Jiménez, Isaac; Gilliland, Douglas; Rossi, François

doi:10.1016/j.toxlet.2013.10.003

Cited by 68 publications

(48 citation statements)

References 45 publications

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“…11,12 ECs do not express typical apoptosis markers, but we can speculate that cells try to activate cell-survival mechanisms, allowing the survival of HUVECs, as suggested for different types of cells after SiO 2 exposure. 33 Interestingly, our results have revealed that autophagy of mitochondria (mitophagy) can be induced by MSNPs as a cellular response for recycling the damaged organelles through molecular mediation associated with change in mitochondrial enzyme activity. 34 Although there was low uptake of 30 nm MSNPs, NO production increased, suggesting that NPs could affect endothelial functionality from outside the cells.…”

Section: Analysis Of Msnp Protein Coronas By Sds-pagementioning

confidence: 76%

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Orlando¹,

Cazzaniga²,

Tringali³

et al. 2017

IJN

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Purpose Mesoporous silica nanoparticles (MSNPs) are excellent candidates for biomedical applications and drug delivery to different human body areas, the brain included. Although toxicity at cellular level has been investigated, we are still far from using MSNPs in the clinic, because the mechanisms involved in the cellular responses activated by MSNPs have not yet been elucidated. Materials and methods This study used an in vitro multiparametric approach to clarify relationships among size, dose, and time of exposure of MSNPs (0.05–1 mg/mL dose range), and cellular responses by analyzing the morphology, viability, and functionality of human vascular endothelial cells and neurons. Results The results showed that 24 hours of exposure of endothelial cells to 250 nm MSNPs exerted higher toxicity in terms of mitochondrial activity and membrane integrity than 30 nm MSN at the same dose. This was due to induced cell autophagy (in particular mitophagy), probably consequent to MSNP cellular uptake (>20%). Interestingly, after 24 hours of treatment with 30 nm MSNPs, very low MSNP uptake (<1%) and an increase in nitric oxide production (30%, P <0.01) were measured. This suggests that MSNPs were able to affect endothelial functionality from outside the cells. These differences could be attributed to the different protein-corona composition of the MSNPs used, as suggested by sodium dodecyl sulfate polyacrylamide-gel electrophoresis analysis of the plasma proteins covering the MSNP surface. Moreover, doses of MSNPs up to 0.25 mg/mL perturbed network activity by increasing excitability, as detected by multielectrode-array technology, without affecting neuronal cell viability. Conclusion These results suggest that MSNPs may be low-risk if prepared with a diameter <30 nm and if they reach human tissues at doses <0.25 mg/mL. These important advances could help the rational design of NPs intended for biomedical uses, demonstrating that careful toxicity evaluation is necessary before using MSNPs in patients.

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Section: Analysis Of Msnp Protein Coronas By Sds-pagementioning

confidence: 76%

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Orlando¹,

Cazzaniga²,

Tringali³

et al. 2017

IJN

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“…Recent research reported that the autophagic activity might be a key mechanism leading to cell survival under 20 nm SiNPs exposure. 57 However, prolonged and uncontrolled autophagy results in harmful cellular dysfunction and also cell death. Lysosome is one of the major intracellular storage sites for SiNPs that enter into cells.…”

Section: Discussionmentioning

confidence: 99%

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

Guo¹,

Yang²,

Li³

et al. 2016

IJN

188

106

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Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury. Significant induction of cytotoxicity as well as oxidative stress, apoptosis, and autophagy was observed in human umbilical vein endothelial cells following the SiNPs exposure ( P <0.05). The oxidative stress was induced by ROS generation, leading to redox imbalance and lipid peroxidation. SiNPs induced mitochondrial dysfunction, characterized by membrane potential collapse, and elevated Bax and declined bcl-2 expression, ultimately leading to apoptosis, and also increased number of autophagosomes and autophagy marker proteins, such as LC3 and p62. Phosphorylated ERK, PI3K, Akt, and mTOR were significantly decreased, but phosphorylated JNK and p38 MAPK were increased in SiNPs-exposed endothelial cells. In contrast, all of these stimulation phenomena were effectively inhibited by N -acetylcysteine. The N -acetylcysteine supplement attenuated SiNPs-induced endothelial toxicity through inhibition of apoptosis and autophagy via MAPK/Bcl-2 and PI3K/Akt/mTOR signaling, as well as suppression of intracellular ROS property via activating antioxidant enzyme and Nrf2 signaling. In summary, the results demonstrated that SiNPs triggered autophagy and apoptosis via ROS-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling in endothelial cells, and subsequently disturbed the endothelial homeostasis and impaired endothelium. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by SiNPs. Furthermore, results hint that the application of antioxidant may provide a novel way for safer use of nanomaterials.

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“…For example, in the deprival of nutrients, cells are undergoing autophagy, which recycles Although some nanoparticles are believed to be biocompatible, it may vary depending on the nature of nanoparticles themselves and the cell types. For example, silica nanoparticles and CdSe/ZnS quantum dots can induce autophagy in A549 cells 6 in synapse, 18 respectively. In our present study, we found Fe 3 O 4 NPs activate autophagy in both normal and malignant blood cells.…”

Section: Discussionmentioning

confidence: 99%

“…6 To find out whether the Fe 3 O 4 NPs induced autophagy in blood cancer cells, leukemia cell lines (OCI-AML2 and K562) and multiple myeloma (MM) cell lines (OPM2, 8226, JJN3) were treated with 100 μg/mL of Fe 3 O 4 NPs with specific modifications including DA, DMSA, or PEG for 9 hours. To view autophagy induced by Fe 3 O 4 NPs, the expression level of LC3-II, a phosphatidylethanolamine (PE)-conjugated form from microtubuleassociated protein 1A/B-LC3 was measured because it is a common indicator of autophagy.…”

Section: Fe 3 O 4 Nps Induce Autophagy In Blood Cancer Cellsmentioning

confidence: 99%

“…Fe 3 O 4 NPs induce autophagy in some cells such as lung epithelial cancer cells and human brain-derived endothelial cells. 5,6 But the biological responses of blood cancer cells to Fe 3 O 4 NPs are unclear. In the present study, we investigated the effects of Fe 3 O 4 NPs with various modifications on blood cells and found that Fe 3 O 4 NPs induce autophagy, which protects myeloma…”

Section: Introductionmentioning

confidence: 99%

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Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex

Shi¹,

Cheng²,

Zhang³

et al. 2014

IJN

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Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with great potentials for various biomedical applications, but their biological activities are largely unknown. In the present study, we found that ferroferric oxide nanoparticles (Fe 3 O 4 NPs) induced autophagy in blood cells. Both naked and modified Fe 3 O 4 NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe 3 O 4 NP-induced autophagy was accompanied by increased Beclin 1 and VPS34 and decreased Bcl-2, thus promoting the formation of the critical complex in autophagy initiation. Further studies demonstrated that Fe 3 O 4 NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe 3 O 4 NPs can induce prosurvival autophagy in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study suggests that caution should be taken when Fe 3 O 4 NPs are used in blood cancer patients.

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Silica nanoparticle uptake induces survival mechanism in A549 cells by the activation of autophagy but not apoptosis

Cited by 68 publications

References 45 publications

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex

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Silica nanoparticle uptake induces survival mechanism in A549 cells by the activation of autophagy but not apoptosis

Cited by 68 publications

References 45 publications

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the&nbsp;Beclin 1/Bcl-2/VPS34 complex

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Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex