RESUMEN
Octahedral rhenium cluster complexes have recently emerged as relevant building blocks for the design of singlet oxygen photosensitizing materials toward biological applications such as blue-light photodynamic therapy. However, their singlet oxygen generation ability as well as biological properties have been studied only superficially. Herein we investigate in detail the singlet oxygen photogeneration, dark and photoinduced cytotoxicity, cellular uptake kinetics, cellular localization and in vitro photoinduced oxidative stress, and photodynamic cytotoxicity of the series of octahedral rhenium cluster complexes [{Re6Q8}(CN)6]4-, where Q = S, Se, Te. Our results demonstrate that the selenium-containing complex possesses optimal properties in terms of absorption and singlet oxygen productivity. These features coupled with the cellular internalization and low dark toxicity lead to the first photoinduced cytotoxic effect observed for a molecular [{M6Q8}L6] complex, making it a promising object for further study in terms of blue-light PDT.
Asunto(s)
Medios de Contraste/farmacología , Complejos de Coordinación/farmacología , Fármacos Fotosensibilizantes/farmacología , Renio/química , Oxígeno Singlete/química , Línea Celular Tumoral , Medios de Contraste/síntesis química , Medios de Contraste/efectos de la radiación , Medios de Contraste/toxicidad , Complejos de Coordinación/síntesis química , Complejos de Coordinación/efectos de la radiación , Complejos de Coordinación/toxicidad , Heterocromatina/efectos de los fármacos , Humanos , Ligandos , Luz , Luminiscencia , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/toxicidadRESUMEN
Octahedral rhenium cluster complexes may have considerable potential as therapeutic and diagnostic drugs due to their luminescent and X-ray contrast properties, as well as their ability to generate singlet oxygen upon photoirradiation. However, their potential biological effects and toxicity in vitro and in vivo are rather far from being understood. Thus, the aim of our research was to study cytotoxicity, intracellular localization and cellular uptake/elimination kinetics in vitro, biodistribution and acute intravenous toxicity in vivo of a complex Na4[{Re6Te8}(CN)6] as the promising compound for biomedical application. The results have demonstrated that the complex penetrates through cell membranes with the maximum accumulation in cells in 24h of incubation and have low toxic effects in vitro and in vivo. The median lethal dose (LD50) of intravenously administrated Na4[{Re6Te8}(CN)6] is equal to 1082±83mg/kg. These findings will be useful for future development of cluster-based agents for different biomedical applications.