Microbubble Sonodestruction Rate as a Metric to Evaluate Sonoporation Efficiency

Objectives The efficiency of sonoporation is directly related to microbubble cavitation and can be dependent on the microbubble sonodestruction rate. The objective of this study was to investigate whether the rate of microbubble sonodestruction can be used as a parameter to develop an implicit dosimetric method for sonoporation efficiency evaluation. Methods To evaluate the rate of microbubble sonodestruction as a function of the ultrasound (US) peak negative ultrasound pressure, 12‐MHz diagnostic US was used in the B‐scan mode. Chinese hamster ovary cells were exposed to therapeutic US at 880 kHz in the absence or presence of microbubbles. The sonoporation efficiency was evaluated by the sonotransfer of bleomycin, a cytotoxic, membrane‐impermeable anticancer drug. Results At a low microbubble sonodestruction rate of 1/τ < 0.5 second–1 (τ providing the time necessary to decrease the microbubble concentration to 37% of its initial value), cell viability remained basically unaffected, but the percentage of sonoporated cells did not reach 10%. At higher microbubble sonodestruction rates, the efficiencies of irreversible and reversible sonoporation started to increase linearly and reached the plateau at 5 seconds–1. Conclusions These results show that the microbubble sonodestruction rate can be used to predict the percentage of reversible and irreversible sonoporation.