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In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()

Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a syner...

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Autores principales: Nguyen, Phuoc Vinh, Hervé-Aubert, Katel, Lajoie, Laurie, Misericordia, Yoann, Chourpa, Igor, David, Stéphanie, Allard-Vannier, Emilie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676141/
https://www.ncbi.nlm.nih.gov/pubmed/36420371
http://dx.doi.org/10.1016/j.ijpx.2022.100139
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author Nguyen, Phuoc Vinh
Hervé-Aubert, Katel
Lajoie, Laurie
Misericordia, Yoann
Chourpa, Igor
David, Stéphanie
Allard-Vannier, Emilie
author_facet Nguyen, Phuoc Vinh
Hervé-Aubert, Katel
Lajoie, Laurie
Misericordia, Yoann
Chourpa, Igor
David, Stéphanie
Allard-Vannier, Emilie
author_sort Nguyen, Phuoc Vinh
collection PubMed
description Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents. In this study, anti-Bcl-xL siRNA were formulated within an EGFR-targeted nanomedicine with scFv ligands (NM-scFv) and its activity was tested in the non-small cell lung cancer (NSCLC) cell line H460. The obtained NMs-scFv anti-Bcl-xL were suitable for intravenous injection with sizes around 100 nm, a high monodispersity level and good siRNA complexation capacity. The nanocomplex's functionalization with anti-EGFR scFv ligands was shown to allow an active gene delivery into H460 cells and led to approximately 63% of gene silencing at both mRNA and protein levels. The NM-scFv anti-Bcl-xL improved the apoptotic activity of cisplatin and reduced the cisplatin IC(50) value in H460 cells by a factor of around three from 0.68 ± 0.12 μM to 2.21 ± 0.18 μM (p < 0.01), respectively, in comparison to that of NM-scFv formulated with control siRNA (p > 0.05).
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spelling pubmed-96761412022-11-22 In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model() Nguyen, Phuoc Vinh Hervé-Aubert, Katel Lajoie, Laurie Misericordia, Yoann Chourpa, Igor David, Stéphanie Allard-Vannier, Emilie Int J Pharm X Research Paper Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents. In this study, anti-Bcl-xL siRNA were formulated within an EGFR-targeted nanomedicine with scFv ligands (NM-scFv) and its activity was tested in the non-small cell lung cancer (NSCLC) cell line H460. The obtained NMs-scFv anti-Bcl-xL were suitable for intravenous injection with sizes around 100 nm, a high monodispersity level and good siRNA complexation capacity. The nanocomplex's functionalization with anti-EGFR scFv ligands was shown to allow an active gene delivery into H460 cells and led to approximately 63% of gene silencing at both mRNA and protein levels. The NM-scFv anti-Bcl-xL improved the apoptotic activity of cisplatin and reduced the cisplatin IC(50) value in H460 cells by a factor of around three from 0.68 ± 0.12 μM to 2.21 ± 0.18 μM (p < 0.01), respectively, in comparison to that of NM-scFv formulated with control siRNA (p > 0.05). Elsevier 2022-11-13 /pmc/articles/PMC9676141/ /pubmed/36420371 http://dx.doi.org/10.1016/j.ijpx.2022.100139 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Nguyen, Phuoc Vinh
Hervé-Aubert, Katel
Lajoie, Laurie
Misericordia, Yoann
Chourpa, Igor
David, Stéphanie
Allard-Vannier, Emilie
In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title_full In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title_fullStr In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title_full_unstemmed In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title_short In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model()
title_sort in vitro synergistic activity of cisplatin and egfr-targeted nanomedicine of anti-bcl-xl sirna in a non-small lung cancer cell line model()
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676141/
https://www.ncbi.nlm.nih.gov/pubmed/36420371
http://dx.doi.org/10.1016/j.ijpx.2022.100139
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