The Self-targeting Ability of Cancer-derived Exosomes to their Parental Cells in a Time and Concentration-Dependent Manner

Abstract Background/Aim: Exosomes have recently attracted research interest as exploitable nano-carriers. However, cell specificity of exosomes toward their targets still needs to be addressed. This study, for the first time, deals with the natural tropism of cancer-derived exosomes towards HER2 positive cells compared to targeted and untargeted HEK-derived exosomes.Methods and Results: Isolated targeted HEK293 and TUBO exosomes were successfully characterized. TUBO cells were treated with various concentrations of fluorescent labeled exosomes at different time points. The tropism of TUBO exosomes was assessed toward other HER2 positive breast cancer cells as well. TUBO-derived exosomes showed 40% uptake, whereas targeted HEK 293 exosomes had lower affinity. By increasing the incubation time, TUBO cells had more time to recognize TUBO exosomes. Fluorimetry analysis revealed that by increasing the dosage of exosomes on HER-2 positive cells, the prominent factor in the attachment was nonspecific physical absorption.Conclusion: Cancer-derived exosomes might be a promising alternative to targeted exosomes as the delivery agent in targeting cancer cells.