The relation of sonoporation efficiency to cavitation metrics

Sonoporation is a biophysical technique, designed to achieve sitepecific and temporally controlled therapeutic agent delivery to cells and tissues. The mechanism behind sonoporation is directly associated to ultrasound (US) induced microbubble (MB) stable and/ or inertial cavitation. In order to achieve sufficient molecular delivery efficiency as well as diminish cell death, the extent of microbubble cavitation must be precisely quantified and controlled. This implies the necessity of a well defined sonoporation dosimetry model relating cavitation metrics to biological outcome. In this study we have evaluated four main sonoporation elements: 1) MB concentration, 2) US attenuation 3) US scattering and 4) anticancer drug, bleomycin, sonotransfer into Chinese hamster ovary cells. We have shown quantified dependencies between US attenuation, root mean square of scattered US signal, MB sonodestruction and bleomycin sonotransfer efficiency in both acoustic pressure and exposure duration scales. In addition to this, we proposed a method to optimize sonoporation efficiency in the temporal domain of the ultrasound field by monitoring either: US attenuation, US scattering or MB concentration decrease to signal background or complete MB destruction levels, respectively. MB concentration dynamics were used to quantify MB sonodestruction rate, while MB cavitation signals, recorded using passive cavitation detection system, were used to quantify attenuation rate and inertial cavitation dose. These metrics have shown strong intercorrelation as well as correlation with bleomycin sonotransfer and cell viability. The latter results imply inertial cavitation to be the key mechanism ir producing efficient cell sonoporation. For the first time, the metric, attenuation rate, was used for sonoporation efficiency and cell viability prognostication. [...]Biologijos katedraVytauto Didžiojo universiteta