201. In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model
- Author
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Phuoc Vinh Nguyen, Katel Hervé-Aubert, Laurie Lajoie, Yoann Misericordia, Igor Chourpa, Stéphanie David, and Emilie Allard-Vannier
- Subjects
NSCLC ,EGFR-targeted nanomedicine ,BcL-xL ,Cisplatin ,Gene delivery ,scFv ,Pharmacy and materia medica ,RS1-441 - 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 0.05).
- Published
- 2022
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