The relation of Bleomycin Delivery Efficiency to Microbubble Sonodestruction and Cavitation Spectral Characteristics.

Martynas Maciulevičius, Mindaugas Tamošiūnas, Mindaugas S Venslauskas, Saulius Šatkauskas

Scientific reports 2020 May 08

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The concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. Microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. Experiments were conducted on Chinese hamster ovary cells coadministered with Sonovue microbubbles. Detailed analysis of the scattering and attenuation temporal functions culminated in quantification of metrics, inertial cavitation dose and attenuation rate, suitable for cavitation control. The exponents, representing microbubble sonodestruction kinetics were exploited to derive dosimetric, microbubble sonodestruction rate. High intracorrelation between empirically-attained metrics defines the relations which indicate deep physical interdependencies within inherent phenomena. Subsequently each quantified metric was validated to be well-applicable to prognosticate the efficacy of bleomycin delivery and cell viability, as indicated by strong overall correlation (R2 > 0.85). Presented results draw valuable insights in sonoporation dosimetry and contribute towards the development of universal sonoporation dosimetry model. Both bleomycin delivery and cell viability reach their respective plateau levels by the time, required to attain total microbubble sonodestruction, which accord with scattering and attenuation decrease to background levels. This suggests a well-defined criterion, feasible through signal-registration, universally employable to set optimal duration of exposure for efficient sonoporation outcome.

Citation

Martynas Maciulevičius, Mindaugas Tamošiūnas, Mindaugas S Venslauskas, Saulius Šatkauskas. The relation of Bleomycin Delivery Efficiency to Microbubble Sonodestruction and Cavitation Spectral Characteristics. Scientific reports. 2020 May 08;10(1):7743