Cyclopentadienyl ruthenium(II) carbosilane metallodendrimers as a promising treatment against advanced prostate cancer

Abstract

In searching for efficient and selective antitumour drugs, a new family of carbosilane metallodendrimers functionalized with [Ru(η⁵-C₅H₅)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) is reported. Experiments of the biophysical characterization showed an ability to interact with biological membranes, as well as with proteins (e.g. human serum albumin) without affecting their usual biological activity. These metallodendrimers possessed potent and selective anticancer activity in vitro in a panel of tumour cell lines. Importantly, the first generation metallodendrimer, bearing 4 Ru(II) complexes, was remarkably active towards resistant prostate cancer cells, inhibiting both cell proliferation and metastasis to bone tissues. Such promising antitumour activity can be further improved when given with docetaxel, with in vitro cytotoxicity being in the nanomolar range. Furthermore, its intravenous administration to an advanced prostate cancer mice model inhibited tumour growth up to 25% and 45% when given 10 mg/kg/week and 7.5 mg/kg/4-5 days, respectively.

Keywords: Antitumour; Combination-therapy; Cyclopentadienyl; Dendrimer; PTA; Ruthenium.