Anticancer activity of a cationic Ru-based nanosystem in a human xenograft model of breast cancer Marialuisa Piccolo1, Maria Grazia Ferraro1, Chiara Tammaro1, Claudia Riccardi2, Francesco Maione1, Marco
Trifuoggi2, Daniela Montesarchio2, Carlo Irace1 and Rita Santamaria1
1Department of Pharmacy, School of Medicine, University of Naples “Federico II”, Via D. Montesano 49,
80131-Naples, Italy.
2Department of Chemical Sciences, University of Naples “Federico II”, Via Cintia 421, 80126-Naples, Italy.
Breast cancer is the second most common cancer worldwide and the leading cause of death in women. The global burden of breast cancers exceeds all other cancers and its incidence is increasing so that the search for novel chemotherapeutic options is nowadays an essential requirement to fight neoplasm subtypes. By exploring new effective metal-based chemotherapeutics, many ruthenium complexes have been recently proposed as anticancer drug candidates, showing ability to impact on diverse cellular targets. In addition, many nanomaterial Ru complexes have been designed and developed into anticancer drugs with interesting beneficial properties. In this context, we have demonstrated the efficacy of a ruthenium (III)-complex (AziRu) incorporated into a cationic nanosystem (HoThyRu/DOTAP), proved to be hitherto one of the most effective within the suite of nucleolipidic formulations we have developed for the in vivo transport of anticancer ruthenium (III)-based drugs. Based on very interesting results on breast cancer cells (BCC), to evaluate the animal biological response to systemic administration of HoThyRu/DOTAP nanosystem, as well as its effects on the progression of breast cancer in vivo, we performed an antitumour study using athymic nude mice bearing human BCC xenografts. In depth analysis of tumour growth shows that HoThyRu/DOTAP significantly inhibits breast cancer cell proliferation in mice, without any sign of toxicity in treated animal group. In addition, molecular biology experiments ex vivo are currently ongoing to deepen the cellular responses and/or resistance to treatments, as well as to support in vivo the activation of specific cell death pathways, i.e. apoptosis and autophagy. On this path, we have validated the efficacy and the safety in vivo of our ruthenium-based candidate drugs in the perspective of novel cancer therapeutic options.
antiproliferative activity in human breast cancer preclinical models by both apoptosis and autophagy activation of
as well in the framework of different molecular pathways leading to cell death in human models of breast cancer,
behind an in-depth microstructural characterization
Following this line, our in vitro and in vivo preclinical investigations suggest that an original strategy based on suitable formulations of ruthenium(III)-complexes, inducing sustained cell death, could
