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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

Abstract : 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 IC50 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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https://hal-univ-tours.archives-ouvertes.fr/hal-03860011
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Submitted on : Friday, November 18, 2022 - 2:34:24 PM
Last modification on : Friday, November 25, 2022 - 3:55:20 AM

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Phuoc Vinh Nguyen, Katel Hervé-Aubert, Laurie Lajoie, Yoann Misericordia, Igor Chourpa, et al.. In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model. International Journal of Pharmaceutics, 2022, pp.122335. ⟨10.1016/j.ijpharm.2022.122335⟩. ⟨hal-03860011⟩

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