On the Acoustic Response of Ultrasonically - stimulated microbubbles and Enhanced Intracellular Uptake of a Fluorescent Molecule

Effectiveness of ultrasound-and-microbubble mediated therapy depends on the acoustic response of microbubbles. In this study, the acoustic response of microbubbles in the absence and presence of cells is measured using integrated cavitation dose (ICD) over harmonics/ultraharmonics/broadband, and correlated with intracellular uptake of a fluorescent marker for varying peak-negative-pressures (PNPs). The ICD was independent of presence of cells. A PNP-threshold of 0.64 MPa was observed for microbubble’s inertial cavitation; stable cavitation (PNPs<0.64MPa) and inertial cavitation (PNPs≥0.64MPa) regimes were identified. Within inertial cavitation regime, a stronger correlation (R2>0.9) was observed between the ICD and FITC-positive cells, whereas, a weaker correlation, ranging from R2=0.59 at 3rd ultra-harmonic to R2 = 0.85 at 2nd ultra-harmonic, was observed under stable cavitation regime. The intracellular uptake, ICD and their correlation is dependent on microbubbles cavitation regime, indicating that ICD shows potential to predict bio-effects induced not only by inertial cavitation but also by stable cavitation of MBs.