Evaluation of the In Vitro and In Vivo Efficacy of Ruthenium Polypyridyl Compounds against Breast Cancer

Lenis-Rojas, Oscar A.; Roma-Rodrigues, Catarina; Fernandes, Alexandra R.; Carvalho, Andreia; Cordeiro, Sandra; Guerra-Varela, Jorge; Sánchez, Laura; Vázquez-García, Digna; López-Torres, Margarita; Fernández, Alberto; Fernández, Jesús J.

The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)(2)(C(12)H(8)N(6)-N,N)][CF(3)SO(3)](2) Ru1 and [{Ru(bipy)(2)}(2)(μ-C(12)H(8)N(6)-N,N)][CF(3)SO(3)](4) Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L(−1). Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.