PhD thesis of Vinh Nguyen (Hybrid nanovectors of siRNA against TNBC)

Summary

This PhD work led to a finalized targeted nanomedicine (NM-scFv) for systemic administration with a size ~100 nm and a slightly positive surface charge. In vitro, our NM-scFv presented a high-performance siRNA protection capacity, as well as a better internalization level into two types of cancer cells (MDA-MB-231 and H460-Luc) than its non-targeted counterpart. Furthermore, an efficient siRNA transfection level between 62% and 68% was achieved with our NM-scFv for different kinds of siRNAs used in this work, including both modeled (anti-GFP and anti-luciferase) and therapeutic (anti-Bcl-xL) ones. Especially, by using anti-Bcl-xL siRNAs as our therapeutic siRNA, a downregulation in this oncoprotein’s expression was observed at both mRNA and protein levels. The Bcl-xL downregulation triggered by our NM-scFv was proven to provide an anticancer synergistic effect with cisplatin in the treatment of non-small lung cancer cells (H460).

Project: NANOTIF, projet Emergence CGO 202

Paper :

• Nguyen et al, Int J Pharm X. 2022 doi: 10.1016/j.ijpx.2022.100139
• Nguyen et al, EJPB. 2020 doi: 10.1016/j.ejpb.2020.10.004