A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies

Abstract

Ru(II) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO₃⁻) ligand based Ru(II) complexes [Ru(N-N)₂(py-SO₃)]⁺ (1–4) were synthesized and studied. All the complexes can undergo fast py-SO₃⁻ ligand dissociation and DNA covalent binding upon visible light irradiation. However, only complex 4 exhibited high photo-induced anticancer activities towards a series of cancer cells, with half maximal inhibitory concentration (IC₅₀) values in 100–300 nM regions and phototoxicity index (PI) values of about 100. In particular, complex 4 can also kill cisplatin resistant SKOV-3 and A549 cancer cells with IC₅₀ values in 200–400 nM regions and PI values of about 50, which should be the first report of Ru(II) based PACT agents that are also effective towards cisplatin resistant cancer cells. Complex 4 exhibited much higher cell uptake and nuclear accumulation levels, which may be the main reasons for its high anticancer activities. The in vivo anticancer experiments indicated that complex 4 can inhibit tumor growth significantly with fewer side effects. Our results may provide guidelines for developing novel photoactivatable Ru(II) anticancer agents.