RESUMEN
We investigated the radiosensitizing effects of Co-NMS, a derivative of nimesulide based on a cobalt carbonyl complex, on malignant glioma cells. In the zebrafish exposed to Co-NMS ranging from 5 to 20 µM, cell death and heat shock protein 70 expression in the brain and neurobehavioral performance were evaluated. Our data showed that Co-NMS at 5 µM did not cause the appreciable neurotoxicity, and thereby was given as a novel radiation sensitizer in further study. In the U251 cells, Co-NMS combined with irradiation treatment resulted in significant inhibition of cell growth and clonogenic capability as well as remarkable increases of G2/M arrest and apoptotic cell population compared to the irradiation alone treatment. This demonstrated that the Co-NMS administration exerted a strong potential of sensitizing effect on the irradiated cells. With regard to the tumor radiosensitization of Co-NMS, it could be primarily attributed to the Co-NMS-derived mitochondrial impairment, reflected by the loss of mitochondrial membrane potential, the disruption of mitochondrial fusion and fission balance as well as redox homeostasis. Furthermore, the energy metabolism of the U251 cells was obviously suppressed by cotreatment with Co-NMS and irradiation through repressing mitochondrial function. Taken together, our findings suggested that Co-NMS could be a desirable drug to enhance the radiotherapeutic effects in glioblastoma patients.
Asunto(s)
Complejos de Coordinación/farmacología , Glioblastoma/radioterapia , Proteínas HSP70 de Choque Térmico/genética , Tolerancia a Radiación/genética , Animales , Apoptosis/genética , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/efectos de la radiación , Cobalto/farmacología , Modelos Animales de Enfermedad , Glioblastoma/genética , Glioblastoma/patología , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/efectos de la radiación , Tolerancia a Radiación/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Pez Cebra/genéticaRESUMEN
Photo-sensitive liposomes have been studied for a few decades and various photo-sensitive triggers have been developed so far. This review offers an overview of the different photo-triggering mechanisms for controlled pulsatile content release from liposomes, which have the potential of finding clinical applications as intelligent drug delivery systems.