Cationic platinum(II) complexes active in vivo as anticancer drugs

Metal-based antitumor drugs are widely used alone or in combination with organic drugs for the treatment of several tumours including some more aggressive cancer types in which other chemotherapeutics resulted inactive. In this regard, very recently, many cationic monofunctional platinum-based anticancer agents were synthesised and characterized thus violating the apparently neutrality demanded for cytotoxic platinum drugs. In comparison with the bifunctional cisplatin, monofunctional compounds display a distinct mechanism of action and a different antitumor profile taking into consideration their ability to effectively bind to DNA and to inhibit transcription both in vitro and in vivo. Our research group has synthesised a series of cationic bulky triamine platinum compounds of general formula [Pt(N-N’)N’Cl]X- where N-N’ is an aminomethylimidazole ligand and the N’ an imidazole ring, both bearing the same alkyl group at the N1 position.1 Their cytotoxicity closed to a completely different pharmacodynamic and cellular uptake behaviour than cisplatin, make them valid candidates for displaying a successful outcome in tumour cell lines still lacking an effective treatment. Their use in association with mesenchymal stromal cells (MSCs) from different tissues was also evaluated in early experiments.2 MSCs proved as innovative tools able to uptake antiproliferative agents (eg.: Paclitaxel, Gemcitabine, Doxorubicin) and release them both as free molecules and exosome associated drugs in a selective way. Moreover, the drug loaded MSCs may be used in vivo as a physiological tool for drug delivery by injecting them both in situ or through systemic administration.