Viability variation of T-cells under ultrasound exposure according to adhesion condition with bubbles.

Abstract

Although cellular immunotherapyis expected as a newcancer treatment, its therapeutic efficiency is limited in solid tumors,because most cells return to the bloodstream rather than adhere to the target site. Therefore, we are motivated to develop a technique to concentrate the cells in the blood flowusing active control of bubble-surrounded cells under ultrasound exposure considering both aspects of cell controllability and viability. We prepared a lipid bubble conjugating ligand to adhere to the surface ofthe T-cells. First, we evaluated the cellcontrollability by retaining the cells on a wall of an artificial blood vesselthrough continuous ultrasound exposure.Next, we investigated the cell viability under ultrasound exposure in a suspension with various bubble concentrations. We estimatedthe concentration of bubbles when the adhesion to the cell surface was saturated.Then,we evaluated the cell viability with various conditions of ultrasound exposure and bubble concentrations.However, it was confirmed that cell damage occurred under conditions that achieved proper control of the cells. Therefore, we exposed the cells to burst waves to reducethe applied ultrasound intensity. Consequently, the significant increase in cell viability wasconfirmed to be inversely proportional to the duty ratio. To retain cellson a vessel wall, determining the appropriate ultrasound condition including sound pressure and waveform is importantto maintain cellviability.