Active control of cell with microbubbles for cellular immunotherapy by acoustic force

Validation of damage on vascular endothelial cells under ultrasound exposure according to adhered situation of bubbles

“…From the results obtained in this research, we elucidated a measure to protect vascular endothelial cells from ultrasound irradiation by varying adhesion situations of LBs. In our preceding studies, [8][9][10][11][12][13][14][15][16][17][18][19][20][21]22) in which we examined active control of micro objects in an artificial blood vessel, we concentrated to irradiate ultrasound to those objects without considering damage on the blood vessels. For the development of therapeutic system including active control of micro objects in blood vessel, the results obtained in this research should be important.…”

“…Since the controllability of BSCs is better for cells with LBs (+) attached onto the cell surfaces than that for cells without LBs according to ultrasound exposure, [10][11][12] we attempted to estimate the degree of adhesion of LBs onto cells by retaining BSCs in flow under ultrasound exposure. Our preceding studies [8][9][10][11][12] suggested that a propelling force to the cell is enhanced by the travelling wave reflected on the surface of the cell because of the boundary in the acoustic impedance. Furthermore, oscillation of the bubbles also enhances the Bjerknes force to propel the cell in the direction of the travelling wave.…”

“…To prevent the diffusion of bubbles after injection into the human body and reduce side effects such as relapse and metastasis inhibitory effects, we have been researching a method to control bubbles [1][2][3][4] using acoustic radiation force. Additionally, we have been researching the manipulation of therapeutic cells to contribute to cellular immunotherapy, [5][6][7] wherein bubble-surrounded cells (BSCs) [8][9][10][11][12][13][14] are produced by attracting bubbles on the cell surfaces to reduce their density. These previous studies have shown that micro objects in blood vessels can be controlled by performing active induction in a bifurcated path using a standing wave 13,14) and active retention in the middle of a path using a travelling wave.…”

Low-frequency HIFU induced cancer immunotherapy: tempting challenges and potential opportunities

“…The use of US alone or the delivery of immune stimulants by US can induce an anti-tumor immune response 166 . The mechanical and cavitation effects produced by FUS can enhance the host's anti-tumor immune response, and deliver genes and antigens to cells to activate the anti-tumor immune response 101 . Compared with HIFU at high temperature aiming for ablating cancer tumor, low-frequency HIFU at low temperature can protect antigen more effectively, stimulate invasion and maturation of DCs in situ, and trigger stronger immune response 167 .…”

“…Cavitation effect is the important physical foundation of USenhanced drug delivery and US-guided gene transfection 100 . One can deliver drugs or transfect genes by using the cavitation effect of US, and assist the tumor cellular immunotherapy 101 . Microbubbles are commonly used as gene or drug barriers.…”