Microbubble-facilitated sonoporation is a rapid, versatile, and non-viral intracellular delivery technique with potential for clinical and ex vivo cell engineering applications. We developed a micropatterning-based approach to investigate the impact of cell shape on sonoporation efficacy. Cationic microbubbles were employed to enhance sonoporation by binding to the cell membrane electrostatically. NIH/3T3 fibroblasts were micropatterned into circle, square, triangle, and rectangle. A two-plate system ensured high-throughput and efficient sonoporation by controlling cationic microbubble-cell attachment. High-speed video microscopy captured the acoustic dynamics of microbubbles under short ultrasound pulses. Our findings reveal that for NIH/3T3 fibroblasts, rectangular cells achieved the highest sonoporation and survival rate, while square-shaped cells demonstrated the greatest propidium iodide uptake. Triangle-shaped NIH/3T3 fibroblasts displayed an initial rise then a plateau in the sonoporation and survival rate as the ultrasound pulse duration increased from 10 cycles to 100 cycles, and then to 200 cycles. Conversely, rectangle-shaped cells showed a decrease followed by a stabilization. Circle-shaped and rectangle-shaped HeLa cells exhibited similar sonoporation outcomes, which were not as effective as NIH/3T3 fibroblasts. This study underscores the significance of cell shape in optimizing sonoporation efficiency and highlights the potential of combining micropatterning with controlled targeting sonoporation to advance intracellular delivery technologies.
Keywords: Cavitation; Cell shape; Intracellular delivery; Sonoporation; Targeted microbubbles.
© 2024. The Author(s).