AVVISO DI SEMINARIO

Prof. Daniela Montesarchio

(University of Napoli Federico II - Department of Chemical Sciences)

Ru(III) complexes for anticancer therapy: the importance of being nucleolipidic

Abstract: Ruthenium complexes are drawing increasing attention as second generation metal-based anticancer agents, with NAMI-A and KP1019 having undertaken advanced clinical trials, and others on the edge to clinical application.

Our recent research interests have been focused on the synthesis and characterization of new nucleolipids, i.e. amphiphilic derivatives of nucleosides used as core scaffolds binding Ru(III) salts and able to self-assemble in aq. solutions into stable nanostructures efficiently internalized into cells.

Using ribo- and deoxyribonucleosides as starting building blocks, a minilibrary of Ru(III) complexes incorporating the NAMI analog AziRu and decorated with diverse hydrophilic and lipophilic chainshas been prepared. Co-aggregated with biocompatible lipids, all these Ru(III)-containing pro-drugs proved to be stable under physiological conditions for months. Detailed microstructural characterization of these co-aggregates, carried out using a combined approach including DLS, EPR and SANS analyses, allowed determining their stability, size and shape. Tested on a panel of human or non-human cells, all the studied Ru(III) complexes showed potent in vitro anticancer activity, and minimal, if not null, toxicity. More recent experiments are aimed at incorporating these nanosystems into theranostic nanoparticles, as well as at further optimizing the general design of the amphiphilic Ru(III)-complexes and their co-aggregates.

The design and synthetic procedures selected to prepare these Ru-containing candidate drugs will be presented, discussing the beneficial effects obtained exploiting this pro-drug approach in the delivery of metal-based drugs.