Marialuisa Piccolo 1, M.G. Ferraro 1, L. Paduano 2, D. Montesarchio 2, R. Santamaria 1, C. Irace 1 1Dept of Pharmacy, "FEDERICO II" University, Naples, Italy. 2Dept of Chemical Sciences, "FEDERICO II" University, Naples, Italy.
Nucleolipidic-based Ru(III) nanosystems induce multiple cell death pathways activation in preclinical models of human breast cancer
According to WHO, breast cancer incidence is increasing and treatment options are limited by toxicity or acquired resistance, so that novel anticancer drugs are required to effective kill specific cancer type. Impaired apoptosis plays a central role in cancer development, limiting the efficacy of conventional therapies. As well, a growing body of evidence is implicating autophagy in both cancer development and therapy. Current research efforts are focused on a deeper understanding of responses to treatments, including cell death pathways activation by novel ruthenium-based drugs, proposed as effective alternative to cisplatin. Aiming at improving their suitability for biomedical applications, we have developed a suite of nucleolipidic Ru(III) complexes preparing stable liposomal nanoformulations endowed with significant antiproliferative activity. Behind an in-depth microstructural characterization, we have focused on the ability of these nanosystems to inhibit proliferation in human breast cancer models. Preclinical investigations revealed cellular responses consistent with both autophagy and apoptosis, suggestive of a possible interplay between different cell death pathways.
