Ultrasound mediated delivery of liposomal doxorubicin in prostate tumor tissue

Combining ultrasound exposure and liposomal encapsulated anti-cancer drugs has beneficial synergistic effects in cancer therapy, although little is known about the underlying mechanisms. This study has focused on investigating the effect of different ultrasound exposures (1 MHz and 300 kHz) on delivery and distribution of liposomal doxorubicin in Balb/c nude mice bearing prostate cancer xenografts. Ultrasound exposure was done 24 h after administration of liposomes to study the effect on liposomes present in extracellular matrix. Optical imaging methods were used to evaluate the effects of the ultrasound exposures both on subcellular microscopic level and macroscopically of organs. Confocal laser scanning microscopy revealed that ultrasound-exposed tumors had increased amounts of released doxorubicin in tumor tissue compared to unexposed control tumors. Image analysis demonstrated an increased distance from blood vessels to areas with liposomes and released doxorubicin in tumors exposed to 1 MHz ultrasound. Whole animal optical imaging showed uptake of liposomes both in normal tissue as well as tumor tissue.