scholarly journals Disruption of Cell Adhesion and Cytoskeletal Networks by Thiol-Functionalized Silica-Coated Iron Oxide Nanoparticles

2020 ◽  
Vol 21 (24) ◽  
pp. 9350
Author(s):  
Karel Královec ◽  
Lucie Melounková ◽  
Marcela Slováková ◽  
Nikola Mannová ◽  
Miloš Sedlák ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Iron Oxide ◽  
Biomedical Applications ◽  
A549 Cells ◽  
Focal Adhesions ◽  
Lung Epithelial Cells ◽  
Cell Cycle Distribution ◽  
Functionalized Silica ◽  
Extracellular Signal ◽  
Cytoskeletal Networks

One of the major obstacles that limits the use of magnetic nanoparticles in biomedical applications is their potential toxicity. In the present study, we evaluated the cytotoxic effects of thiol-functionalized silica-coated iron oxide (Fe3O4@SiO2-SH) nanoparticles using human lung epithelial cells A549. We investigated the effect of Fe3O4@SiO2-SH nanoparticles on the cell viability, proliferation, cell cycle distribution, adhesion, apoptosis, and the orientation of the cytoskeletal networks, as well as on expression of proteins involved in cell death, cell survival, and cell adhesion. We demonstrated that exposure of A549 cells to Fe3O4@SiO2-SH nanoparticles resulted in severe disruption of the actin microfilaments and microtubule cytoskeleton and reduced the size of focal adhesions. Furthermore, cell adhesion was significantly affected as well as the phosphorylation of focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), and p38. Our findings highlight the need for in-depth cytotoxic evaluation of nanoparticles supporting their safer use, especially in biomedical applications.

scholarly journals Superparamagnetic Iron Oxide Nanoparticles Modified with Silica Layers as Potential Agents for Lung Cancer Treatment

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1076 ◽  
Author(s):  
Katarzyna Reczyńska ◽  
Marta Marszałek ◽  
Arkadiusz Zarzycki ◽  
Witold Reczyński ◽  
Kamil Kornaus ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
A549 Cells ◽  
Superparamagnetic Iron Oxide ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Lung Epithelial Cells ◽  
Bet Surface Area ◽  
Oxide Nanoparticles ◽  
Iron Release ◽  
Silica Layers

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising drug delivery carriers and hyperthermia agents for the treatment of cancer. However, to ensure their safety in vivo, SPIONs must be modified in order to prevent unwanted iron release. Thus, SPIONs were coated with silica layers of different morphologies: non-porous (@SiO2), mesoporous (@mSiO2) or with a combination of non-porous and mesoporous layers (@SiO2@mSiO2) deposited via a sol–gel method. The presence of SiO2 drastically changed the surface properties of the nanoparticles. The zeta potential changed from 19.6 ± 0.8 mV for SPIONs to −26.1 ± 0.1 mV for SPION@mSiO2. The Brunauer–Emmett–Teller (BET) surface area increased from 7.54 ± 0.02 m2/g for SPIONs to 101.3 ± 2.8 m2/g for SPION@mSiO2. All types of coatings significantly decreased iron release (at least 10 fold as compared to unmodified SPIONs). SPIONs and SPION@mSiO2 were tested in vitro in contact with human lung epithelial cells (A549 and BEAS-2B). Both nanoparticle types were cytocompatible, although some delay in proliferation was observed for BEAS-2B cells as compared to A549 cells, which was correlated with increased cell velocity and nanoparticles uptake.

scholarly journals p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia

2004 ◽  
Vol 286 (4) ◽  
pp. L826-L833 ◽  
Author(s):  
Charles S. Powell ◽  
Marcienne M. Wright ◽  
Robert M. Jackson
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Protective Effects ◽  
Hypoxia Exposure ◽  
Extracellular Signal ◽  
Lung Epithelial ◽  
Mitogen Activated Protein ◽  
Chemical Inhibition

Lung epithelial cells produce increased reactive oxygen species (ROS) after hypoxia exposure, and they are more susceptible after hypoxia to injury by agents that generate superoxide [[Formula: see text]; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)]. Cellular GSH and MnSOD both decrease in hypoxic lung epithelial cells, altering the redox state. Because ROS participate in signaling pathways involved in cell death or survival, we tested the hypothesis that mitogen-activated protein kinases (MAPK) were involved in a protective response against cellular injury during reoxygenation. Human lung epithelial A549 cells were incubated in hypoxia (<1% O2 for 24 h) and then reoxygenated by return to air. p38mapk and MKK3 phosphorylation both decreased after hypoxia. During reoxygenation, cells were incubated with DMNQ (0–50 μM), a redox cycling quinone that produces [Formula: see text]. Hypoxia preexposure significantly increased epithelial cell lysis resulting from DMNQ. Addition of the p38mapk inhibitors SB-202190 or SB-203580 markedly increased cytotoxicity, as did the mitogen/extracellular signal-regulated kinase (MEK) 1/2 inhibitor PD-98059 (all 10 μM), suggesting a protective effect of downstream molecules activated by the kinases. Transfection of A549 cells with a dominant active MKK3 plasmid (MKK3[Glu]) partially inhibited cytolysis resulting from DMNQ, whereas the inactive MKK3 plasmid (MKK3[Ala]) had less evident protective effects. Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from [Formula: see text].

Iron Oxide Nanoparticles: An Insight into their Biomedical Applications

2015 ◽  
Vol 22 (15) ◽  
pp. 1808-1828 ◽  
Author(s):  
Diana Couto ◽  
Marisa Freitas ◽  
Felix Carvalho ◽  
Eduarda Fernandes
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Biomedical Applications ◽  
Oxide Nanoparticles ◽  
Insight Into

scholarly journals The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Hosami ◽  
Azadeh Manayi ◽  
Vahid Salimi ◽  
Farshad Khodakhah ◽  
Mitra Nourbakhsh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Caspase 3 ◽  
Cannabis Sativa ◽  
A549 Cells ◽  
Echinacea Purpurea ◽  
G1 Phase ◽  
Cell Cycle Distribution ◽  
Cb2 Receptor ◽  
Anti Cancer

Abstract Background Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study. Methods The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit. Results Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells. Conclusions The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents. Graphical abstract

scholarly journals Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5091
Author(s):  
Acharya Balkrishna ◽  
Siva Kumar Solleti ◽  
Sudeep Verma ◽  
Anurag Varshney
Keyword(s):  
Herbal Medicine ◽  
High Performance ◽  
Normal Skin ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Spike Protein ◽  
Protective Effects ◽  
Cell Degeneration ◽  
Zebrafish Model ◽  
Tnf Α

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV–V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1β induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Bio-inspired encapsulation and functionalization of iron oxide nanoparticles for biomedical applications

2020 ◽  
Vol 122 ◽  
pp. 109371 ◽  
Author(s):  
Samson O. Aisida ◽  
Paul A. Akpa ◽  
Ishaq Ahmad ◽  
Ting-kai Zhao ◽  
M. Maaza ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Biomedical Applications ◽  
Oxide Nanoparticles

scholarly journals Convenient synthesis of heterobifunctional poly(ethylene glycol) suitable for the functionalization of iron oxide nanoparticles for biomedical applications

2013 ◽  
Vol 23 (17) ◽  
pp. 5006-5010 ◽  
Author(s):  
Solène Passemard ◽  
Davide Staedler ◽  
Lucia Učňová ◽  
Guillaume Stéphane Schneiter ◽  
Phally Kong ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Ethylene Glycol ◽  
Iron Oxide Nanoparticles ◽  
Biomedical Applications ◽  
Oxide Nanoparticles ◽  
Poly Ethylene Glycol ◽  
Convenient Synthesis ◽  
Poly Ethylene

Dynamic Investigation of Interaction of Biocompatible Iron Oxide Nanoparticles with Epithelial Cells for Biomedical Applications

2013 ◽  
Vol 9 (9) ◽  
pp. 1556-1569 ◽  
Author(s):  
Alice Panariti ◽  
Barbara Lettiero ◽  
Rodica Alexandrescu ◽  
Maddalena Collini ◽  
Laura Sironi ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Epithelial Cells ◽  
Iron Oxide Nanoparticles ◽  
Biomedical Applications ◽  
Oxide Nanoparticles ◽  
Dynamic Investigation
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