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