Effects Of Cell Cycle On Ultrasound Combined With Microbubble-Mediated Drug Transfection

Microbubble-mediated sonoporation has a great potential for targeted drug/gene-transfection.Compared with other methods,it can not only effectively improve the efficiency of targeted drug transfection,but also reduce the side effect on normal tissues nearby.However,the mechanism underlying microbubble-facilitated gene/drug transfection is still under clear,and the influence cell-cycle-phases on microbubble-mediated sonoporation remains to be elucidated.In this study,HeLa cells were synchronized to G1,S and G2/M phases using lovastatin,mimosine and nocodazole,respectively.Their morphology and stiffness were evaluated with atomic force microscopy(AFM).Then,ultrasound sonication was applied to synchronized cells with the presence of microbubbles,and the drug transfection efficiency and cell viability were analyzed by the flow cytometry.The result showed that,the orders of cell volume and Young's modulus were G1<S<G2/M and G1>G2/M>S,respectively.Due to the effect of cell volume,the drug transfection efficiency follows the sequence that G1<S<G2/M.It was also noticed that,under the influence of Young's Modulus,the order of change of drug transfection efficiency and change rate of cell viability for three phases was G1<G2/M<S with the increase of ICD.In this paper,we have found the relations between drug transfection efficiency for different cell-cycle-phases,which is important for better understanding the mechanisms underlying microbubble-facilitated gene/drug transfection.The results of the current work might be beneficial for controlling and optimizing the applications of microbubble sonoporation in the field of therapeutic ultrasound.