Ultrasound-Mediated Targeted Drug Delivery in T-Cells

Abstract

Ultrasound in mega-hertz range, interacting with the gas encapsulated micron- sized bubbles makes temporary mini pores on the nearby cell membranes by the shear stress. Thus, specific drugs could be delivered inside the cells via these mini holes. This process is called the sonoporation and is one promising non-viral approach for the targeted drug and gene delivery. Small interference RNA (siRNA) has been used to silence expression of molecules in cells in vitro. The delivery of siRNA to different tissues have been limiting factors for their use as therapeutics. Similarly, T-cells are extremely difficult to be transfected. Considering the fact that small interference RNA (siRNA) delivery, particularly in T-cells have been challenging in medical field by various viral and non-viral methods, we have performed in-vitro experiments using this technique to deliver siRNA molecules inside the mouse and human T-cells. We have optimized the ultrasound parameters (acoustic frequency intensity, duty cycle, time duration of ultrasound excitation), concentration of DEFINITY® microbubbles and siRNA per sample to provide efficient siRNA drug delivery in human and mice T-cells.