Intracorporeal Sonoporation-Induced Drug/Gene Delivery Using a Catheter Ultrasound Transducer

Ultrasound (US) has been recently demonstrated promising in cancer immunotherapy. By virtue of microbubble-mediated cavitation, US can induce temporary pores in the cell membrane to enhance drug/gene delivery and this process is termed sonoporation. Currently, the typical US transducer for sonoporation is extracorporeal, lacking the ability to target lesions behind bones and fat efficiently, as well as to inject microbubbles (MBs) and nucleic acids into the US treatment zone simultaneously. These issues can decrease the drug/gene delivery effectiveness and increase the undesired systemic toxicity for cancer immunotherapy. Here we demonstrated an 800 kHz miniaturized US transducer for intracorporeal sonoporation-induced drug/gene delivery. Acoustic simulation using k-Wave toolbox was carried out to explore the 800 kHz US wave propagation in a 384-well cell culture plate. In-vitro sonoporation tests using human embryonic kidney (IIEK) 293T cells and green fluorescent protein-luciferase (GFP-LUC) encoded plasmid DNA were conducted with various sonication parameters (i.e., 0.1 - 0.7 MPa peak-negative pressure; 20 - 2000 cycle number). The LUC assay demonstrated a significantly enhanced transfection, indicating the developed catheter transducer is promising for intracorporeal sonoporation-induced drug/gene delivery, such as intratumoral immunotherapy.