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

Phuoc Vinh Nguyen (1, 2) , Katel Hervé-Aubert (2) , Laurie Lajoie (3) , Yoann Misericordia (2) , Igor Chourpa (2) , Stéphanie David (2) , Emilie Allard-Vannier (2)

1 VNU-HCM - Vietnam National University, Ho Chi Minh City / Đại học Quốc gia TP. Hồ Chí Minh
2 NMNS - Nanomédicaments et Nanosondes
3 UMR ISP - Infectiologie et Santé Publique

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).

Mots clés: BcL-xL; EGFR-targeted nanomedicine; NSCLC; cisplatin; gene delivery; scFv

Domaines: Cancer; Ingénierie biomédicale

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: X, 2022, 4, pp.100139. ⟨10.1016/j.ijpx.2022.100139⟩. ⟨hal-03860011⟩