RESUMEN
Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10's biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.
Asunto(s)
Fibroblastos , Óxido Nítrico , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Óxido Nítrico/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Rutenio/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/química , Relación Dosis-Respuesta a Droga , LuzRESUMEN
Based on Boolean logic, molecular keypad locks secure molecular information, typically with an optical output. Here we investigate a rare example of a molecular keypad lock with a chemical output. To this end, the light-activated release of biologically important nitric oxide from a ruthenium complex is studied, using proton concentration and photon flux as inputs. In a pH-dependent equilibrium, a nitritoruthenium(II) complex is turned into a nitrosylruthenium(II) complex, which releases nitric oxide under irradiation with visible light. The precise prediction of the output nitric oxide concentration as function of the pH and photon flux is achieved with an artificial intelligence approach, namely the adaptive neuro-fuzzy inference system. In this manner an exceptionally high level of control over the output concentration is obtained. Moreover, the provided concept to lock a chemical output as well as the output prediction may be applied to other (photo)release schemes.