Effect of the irradiation on Neuroblastoma-derived microvesicles: A physical and biological investigation

Radiation therapy is one of the most commonly used therapeutic approaches for cancer treatment. Despite the undoubted benefits obtained with its application, numerous side effects occur, mainly related to the ability of irradiated cells to send messages to the un-irradiated ones (bystander effect). A key role in the transmission of bystander effects is played by micro-vesicles released from irradiated cells. Within this framework, particular attention was given to exosomes, vesicles with diameter smaller than 100 nm, whose composition consists in a cargo (protein and nucleic acids) and a double layer membrane (lipids and protein). Exosomes secreted by cancer cells after irradiation show different biochemical and biological features. The modification of secreted exosomes is suggested to be associated with unwanted radiotherapy effects. A major challenge is to establish the correlation between physical property and messages carried by micro-vesicles, for a potential use of exosomes as biomarkers for side effects of radiotherapy. In this work, we report that micro-vesicles secreted by X rays-irradiated neuroblastoma cells stimulate proliferation and confer radio-resistance, in a greater extent than those secreted by un-irradiated cells. The micro-vesicles were analyzed according to their morphology, size and their zeta-potential. The obtained results suggest that the surface charge distribution allows distinguishing the vesicles of the control neuroblastoma from that irradiated.