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; Katel Hervé-Aubert; Laurie Lajoie; Yoann Misericordia; Igor Chourpa; Stéphanie David; Emilie Allard-Vannier

doi:10.1016/j.ijpx.2022.100139

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

Int J Pharm X. 2022 Nov 13:4:100139. doi: 10.1016/j.ijpx.2022.100139. eCollection 2022 Dec.

Authors

Phuoc Vinh Nguyen^{1

2}, Katel Hervé-Aubert¹, Laurie Lajoie³, Yoann Misericordia¹, Igor Chourpa¹, Stéphanie David¹, Emilie Allard-Vannier¹

Affiliations

¹ EA6295 Nanomédicaments et Nanosondes, Université de Tours, Tours, France.
² School of Medicine, Vietnam National University Ho Chi Minh city, Ho Chi Minh city, Viet Nam.
³ ISP UMR1282, INRAE, équipe BioMAP, Université de Tours, Tours, France.

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).

Keywords: BcL-xL; BcL-xL, B-cell lymphoma-extra large; Cisplatin; EGFR, epidermal growth factor receptor; EGFR-targeted nanomedicine; Gene delivery; NSCLC; NSCLC, non-small cell lung cancer; scFv; scFv, single chain variable fragment.