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The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages

INTRODUCTION: This study is aimed at investigating the immunological response after treating THP-1 cells with gold nanorods conjugated with a phosphatidylinositol 3-kinase (PI3Kα) inhibitor. Methodology. Gold nanorods were synthesized and functionalized with cholesterol-PEG-SH moiety, and the treatm...

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Autores principales: Abuarqoub, Duaa, Mahmoud, Nouf N., Zaza, Rand, Abu-Dahab, Rana, Khalil, Enam A., Sabbah, Dima A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904913/
https://www.ncbi.nlm.nih.gov/pubmed/35284577
http://dx.doi.org/10.1155/2022/6031776
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author Abuarqoub, Duaa
Mahmoud, Nouf N.
Zaza, Rand
Abu-Dahab, Rana
Khalil, Enam A.
Sabbah, Dima A.
author_facet Abuarqoub, Duaa
Mahmoud, Nouf N.
Zaza, Rand
Abu-Dahab, Rana
Khalil, Enam A.
Sabbah, Dima A.
author_sort Abuarqoub, Duaa
collection PubMed
description INTRODUCTION: This study is aimed at investigating the immunological response after treating THP-1 cells with gold nanorods conjugated with a phosphatidylinositol 3-kinase (PI3Kα) inhibitor. Methodology. Gold nanorods were synthesized and functionalized with cholesterol-PEG-SH moiety, and the treatment groups were as follows: nanocomplex (a drug-conjugated gold nanorods), free drug (phosphatidylinositol 3-kinase (PI3Kα) inhibitor), and GNR (the nanocarrier; cholesterol-coated gold nanorods). THP-1 cells were differentiated into macrophages and characterized by measuring the expression of macrophage surface markers by flow cytometry. Then, differentiated cells were activated by lipopolysaccharide (LPS). Afterwards, activated macrophages were treated with the different treatments: nanocomplex, free drug, and GNR, for 24 hrs. After treatment, the production of the inflammatory cytokines measured at gene and protein levels by using qPCR and CBA array beads by flow cytometry. RESULTS: Our results show that THP-1 cells were successfully differentiated into macrophages. For inflammatory cytokine expression response, nanocomplex and free drug showed the same expression level of cytokines at gene level, as the expression of IL-1β, IL-6, and TNF-α was significantly downregulated (p < 0.0005, p < 0.0005, p < 0.00005), respectively, while IL-8, IL-10, and TGF-β were all upregulated in a significant manner for nanocomplex (p < 0.00005, p < 0.00005, p < 0.00005) and free drug treatment group (p < 0.00005, p < 0.05, p < 0.05) compared to the control untreated group. While in the GNR group, IL-6 and TNF-α were downregulated (p < 0.005, p < 0.00005), and IL-12p40 (p < 0.00005) was upregulated all in a statistically significant manner. While at protein level, cells were treated with our nanocomplex: IL-1β, IL-6, TNF-α, and IL-12p70 and were significantly decreased (p < 0.00005,p < 0.005,p < 0.05,p < 0.00005), and IL-10 was found to be significantly increased in culture compared to the untreated control group (p < 0.005). For free drug; IL-1β and IL-12p70 were significantly decreased (p < 0.00005, p < 0.00005), while a significant increase in the secretion levels of IL-10 only was noticed compared to the untreated group (p < 0.005). For GNR treatment groups, IL-1β, TNF-α, and IL-12p70 were significantly decreased (p < 0.00005, p < 0.05, p < 0.00005). CONCLUSION: We can conclude that our nanocomplex is a potent effector that prevents tumoral progression by activating three main immunological strategies: switching the surface expression profile of the activated macrophages into a proinflammatory M1-like phenotype, downregulating the expression of proinflammatory cytokines, and upregulating the expression level of anti-inflammatory cytokines.
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spelling pubmed-89049132022-03-10 The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages Abuarqoub, Duaa Mahmoud, Nouf N. Zaza, Rand Abu-Dahab, Rana Khalil, Enam A. Sabbah, Dima A. J Immunol Res Research Article INTRODUCTION: This study is aimed at investigating the immunological response after treating THP-1 cells with gold nanorods conjugated with a phosphatidylinositol 3-kinase (PI3Kα) inhibitor. Methodology. Gold nanorods were synthesized and functionalized with cholesterol-PEG-SH moiety, and the treatment groups were as follows: nanocomplex (a drug-conjugated gold nanorods), free drug (phosphatidylinositol 3-kinase (PI3Kα) inhibitor), and GNR (the nanocarrier; cholesterol-coated gold nanorods). THP-1 cells were differentiated into macrophages and characterized by measuring the expression of macrophage surface markers by flow cytometry. Then, differentiated cells were activated by lipopolysaccharide (LPS). Afterwards, activated macrophages were treated with the different treatments: nanocomplex, free drug, and GNR, for 24 hrs. After treatment, the production of the inflammatory cytokines measured at gene and protein levels by using qPCR and CBA array beads by flow cytometry. RESULTS: Our results show that THP-1 cells were successfully differentiated into macrophages. For inflammatory cytokine expression response, nanocomplex and free drug showed the same expression level of cytokines at gene level, as the expression of IL-1β, IL-6, and TNF-α was significantly downregulated (p < 0.0005, p < 0.0005, p < 0.00005), respectively, while IL-8, IL-10, and TGF-β were all upregulated in a significant manner for nanocomplex (p < 0.00005, p < 0.00005, p < 0.00005) and free drug treatment group (p < 0.00005, p < 0.05, p < 0.05) compared to the control untreated group. While in the GNR group, IL-6 and TNF-α were downregulated (p < 0.005, p < 0.00005), and IL-12p40 (p < 0.00005) was upregulated all in a statistically significant manner. While at protein level, cells were treated with our nanocomplex: IL-1β, IL-6, TNF-α, and IL-12p70 and were significantly decreased (p < 0.00005,p < 0.005,p < 0.05,p < 0.00005), and IL-10 was found to be significantly increased in culture compared to the untreated control group (p < 0.005). For free drug; IL-1β and IL-12p70 were significantly decreased (p < 0.00005, p < 0.00005), while a significant increase in the secretion levels of IL-10 only was noticed compared to the untreated group (p < 0.005). For GNR treatment groups, IL-1β, TNF-α, and IL-12p70 were significantly decreased (p < 0.00005, p < 0.05, p < 0.00005). CONCLUSION: We can conclude that our nanocomplex is a potent effector that prevents tumoral progression by activating three main immunological strategies: switching the surface expression profile of the activated macrophages into a proinflammatory M1-like phenotype, downregulating the expression of proinflammatory cytokines, and upregulating the expression level of anti-inflammatory cytokines. Hindawi 2022-02-10 /pmc/articles/PMC8904913/ /pubmed/35284577 http://dx.doi.org/10.1155/2022/6031776 Text en Copyright © 2022 Duaa Abuarqoub et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Abuarqoub, Duaa
Mahmoud, Nouf N.
Zaza, Rand
Abu-Dahab, Rana
Khalil, Enam A.
Sabbah, Dima A.
The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title_full The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title_fullStr The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title_full_unstemmed The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title_short The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages
title_sort in vitro immunomodulatory effects of gold nanocomplex on thp-1-derived macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904913/
https://www.ncbi.nlm.nih.gov/pubmed/35284577
http://dx.doi.org/10.1155/2022/6031776
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