Increased accumulation of paclitaxel and doxorubicin in proliferating capillary cells and prostate cancer cells following ultrasound exposure

IntroductionWe have previously reported enhanced cytotoxic effects of both doxorubicin and antisense oligonucleotides using an optimized ultrasound regime of a single 10 s exposure in burst-mode (4 MHz, 32 W/cm2(SaTa), 50 ms burst period) in both PC3 (prostate cancer) cells and angiogenic Huvec (human umbilical cord endothelial cells). The objective of this study was to investigate the effect of ultrasound on the cellular uptake of both hydrophilic agents (rhodamine R123, doxorubicin hydrochloride and mannitol) and hydrophobic agents (rhodamine R6G and paclitaxel) using the same 4 MHz ultrasound exposure system.MethodsPC3 cells and Huvec were incubated with solutions of radioactive or fluorescent compounds for 1 h and ultrasound was then applied to cells. Following washing and lysis of cells, the degree of drug uptake was measured using liquid scintillation counting or fluorescence spectroscopy.ResultsUltrasound exposure resulted in the enhanced uptake of both hydrophilic and hydrophobic compounds into cells. For paclitaxel, approximately 100% increased uptake was observed when the drug was encapsulated in a nanoparticulate micellar formulation compared to approximately 50% for free drug.ConclusionsThe 4 MHz, 32 W/cm2 ultrasound exposure regime (using burst-mode with 50 ms burst period) allows for the enhanced uptake of both water soluble and insoluble compounds into proliferating cancer and angiogenic cells.

► An optimized ultrasound regime (4 MHz, 32 W/cm2, 50 ms burst period) increased the uptake of both hydrophilic and hydrophobic compounds into cells.
► The ultrasound-induced enhanced uptake of compounds was similar for both capillary endothelial cells and prostate cancer cells.
► The enhanced uptake for paclitaxel formulated in polymeric micelles was greater than that observed for free drug.
► This ultrasound regime may be used in cancer therapy allowing for increased drug uptake in cancer cells in irradiated tumors.