Estimate the delivery efficiency in cancer cells of drug-loaded microbubbles with US and IVIS

In combination with drug loaded microbubbles (MBs), increased local concentrations can be achieved by the ultrasound (US) targeted drug release and transiently increased capillary permeability at the site of MBs destruction. To prove the mechanism of US mediated release of drug loaded MBs, this study designs a new model with a method combining the high frequency US image and in vivo bioluminescence imaging system (IVIS). The mechanism of US mediated release of luciferin loaded MBs through blood vessel to targeted cells was investigated. The luciferin loaded MBs with a 1591 nm diameter, 2.48×10 ⁹ bubbles/ml concentration were produced. The concentration of luciferin encapsulated in the shell was 1.48×10 ^-10 mg/bubble. In vitro and in vivo experiments of US mediated release of luciferin loaded MBs with IVIS were performed. The efficiency of US mediated release of luciferin loaded MBs in 4T1-luc2 tumor bearing mice was estimated. The photon number of tumor with luciferin loaded MBs in IVIS image is 2.48×10 ⁵ and the photon number of tumor with US mediated release of luciferin loaded MBs is 1.04×10 ⁷. The amount of photon in US mediated release of luciferin loaded MBs is increased obviously and the injection dose of luciferin with US mediated release of luciferin loaded MBs is reduced. The delivery efficiency of US mediated release is higher than non US mediated release with luciferin loaded MBs.