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Title: Liposomes as valuable drug delivery systems for siRNA and Hsp90 inhibitors to target triple negative breast tumors

Juliette Vergnaud-Gauduchon

Universite Paris-Sud, France

Biography

Juliette Vergnaud is associate professor. She obtained her PharmD in 2002 and her PhD in 2005 at Université de Caen-Basse-Normandie, France (Dr. Brigitte Sola’s Lab). She obtained her Ability to conduct researches in 2017. In 2006, Juliette Vergnaud was recruited at Université d’Auvergne (Clermont-Ferrand, France) in the M-P Vasson’s lab. Her research work focused on the immune cell functions during nutritional intervention. In 2010, she joined UMR 8612 and the Elias Fattal’s team. Her main project aims to target cancer cells at the cellular and subcellular levels using liposomes encapsulating inhibitors of Hsp90 family proteins. She is the author (and co-author) of 32 publications.

Abstract

Triple Negative Breast Cancers (TNBC) are not efficiently treated by specific targeted therapy. New strategies must be envisaged and nanocarriers appear as good candidates to overcome low efficacy of drugs or resistance to treatment. CD44 is found overexpressed in many tumors, such as TNBC, making this an attractive receptor for therapeutic targeting. Besides, HSP90 inhibitors have been shown as promising molecules to treat cancer. Here we show our both drug delivery approaches to target TNBC. First, using for the first time an anti-CD44 aptamer as targeting ligand, a unique non-cationic liposome-based siRNA delivery system was evaluated for the silencing of the luciferase reporter gene (luc2) in a TNBC breast cancer model in vitro and in vivo (orthotopic model). Secondly, we succeeded to use the inhibition of the chaperone Hsp90 at the level of its C-terminal domain against breast cancer. Encapsulated in liposomes, a promising Hsp90i derived from Novobiocin (6BrCaQ) displayed a good activity on breast and prostate cancer cells in vitro and synergized with doxorubicin. In the in vivo orthotopic TNBC model we evaluated the anti-tumor activity of these liposomes. Our work gives evidences that liposomes are powerful tools to target CD44 positive cells in resistant TNBC breast tumors and to deliver not only siRNA but also an anti-tumor but poorly soluble inhibitor of HSP90.
Audience take away:
• The interest of liposomes in the delivery of molecules of different natures and in the selective targeting of cancer cells in vivo with a good efficacy
• A new promising molecule that is difficult to administer alone due to poor water solubility as Hsp90 inhibitors.
• How aptamers can supplant ligands conventionally found on nanovectors