Abstract
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.
Highlights
Cell sonoporation process is initiated by cavitating MBs, directly exposed to US irradiation
The authors have calculated average root mean square (RMS) values of US scattered by MBs and discovered that RMS strongly correlated with hemolysis as well as platelet sonolysis
Chen et al have advanced the field of implicit dosimetry by proposing the metric, inertial cavitation dose (ICD), defined as the integral of RMS of scattered US signal cumulated in exposure duration scale[38,41]
Summary
Cell sonoporation process is initiated by cavitating MBs, directly exposed to US irradiation. Inertial cavitation occurs at higher acoustic pressures when MBs rapidly grow in size and violently collapse This results in US field that has components in broad frequency range, causing a phenomenon called “broadband noise” to emerge[17,18,19,20]. Chen et al have advanced the field of implicit dosimetry by proposing the metric, inertial cavitation dose (ICD), defined as the integral of RMS of scattered US signal cumulated in exposure duration scale[38,41]. The latter was used to prognosticate erythrocyte hemolysis in a variety of physical conditions applied. US attenuation measurements have been successfully applied to evaluate MB sonodestruction dynamics[1,59,60], determine the acoustic characteristics of different MB types[61,62,63], relate sonoporation efficiency to the attenuation level[64] as well as to determine the resonant frequency of MBs58,65
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