Séminaire Simona Mura (IGPS)

Breaking barriers: nanomedicine fate from administration target site

S. Mura, Orsay/France

Nanoscale systems for drug delivery have the potential to overcome the limitations of conventional treatments, thus providing a solution to unmet medical needs.

The therapeutic benefits of this approach have led to the commercialization of more than 50 nanomedicines such as doxorubicin-loaded liposomes (Doxil®, Myocet®), paclitaxel-albumin nanoparticles (Abraxane®), and more recently, lipid carriers for the delivery of siRNA (Patisiran/ONPATTRO®) or mRNA (BioNTech/Pfizer and Moderna COVID-19 vaccines).

Although these results provide clear evidence of the potential of nanomedicines for the efficient delivery of chemotherapeutics, there is still a substantial gap between the favorable preclinical results and the real clinical performances.

The introduction of nanomedicine in the clinic has been partly hampered by the lack of effective delivery to the target in vivo. Among the multiplicity of imputable factors, a major role can be attributed to: (i) the modifications undergone by nanomedicines after interaction with molecules/proteins in the bloodstream that endow them with a specific molecular signature and (ii) the numerous biological barriers that these nanomedicines must cross (e.g., the vascular endothelium, the tumor extracellular matrix, etc…).

In this context, it is necessary to have a clearer comprehension of their fate after administration.

Our research group is focusing on this topic, and we are developing different tools to investigate and better understand the barriers encountered nanomedicines both in the circulation after intravenous administration and, after extravasation, in the complex tumor microenvironment.

During this talk, the most significant results we have obtained will be presented

Literature:

[1] Sobot D, Mura S, Yesylevskyy SO, Dalbin L, Cayre F, Bort G, Mougin J, Desmaële D, Lepetre-Mouelhi S, Pieters G, Andreiuk B, Klymchenko AS, Paul JL, Ramseyer C, Couvreur P. Nature Comm 2017, 8, 15678

[2] Lazzari G, Nicolas V, Matsusaki M, Akashi M, Couvreur P, Mura S. Acta Biomaterialia 2018, 78, 296.

[3] Bidan N, Dunsmore G, Ugrinic M, Bied M, Moreira M, Deloménie C, Ginhoux F, Blériot C, de la Fuente M, Mura S. Drug Deliv Transl Res. 2023