Combination of ultrasound and bubble liposome enhance the effect of doxorubicin and inhibit murine osteosarcoma growth

Abstract

If ultrasound (US) is applied to cells, permeability across the cell membrane temporarily increases, making it easier for drugs to be taken into the cells from around the cell membrane. Moreover, when used in combination with Bubble liposome (BL: liposomes which entrap an ultrasound imaging gas), even low-power ultrasound can facilitate drug delivery into cells. In the present study, we constructed a new drug delivery system (DDS) involving concomitant use of US and BL with doxorubicin (DOX), a key drug in the chemotherapy of osteosarcoma, and demonstrated both in vitro and in vivo that it markedly inhibited the proliferation of osteosarcoma cells. Furthermore, this system achieved an equivalent antitumor effect at about 1/5 the dose of antitumor agent employed in monotherapy with DOX. These findings suggest the possibility of reduction of adverse events. In this experiment, US and liposomes were tested, both of which are already in use in clinical practice. US and liposomes are both very safe in the body. The DDS composed of these elements we designed can be applied in simple and site-specific fashion and is therefore promising as a new, clinically feasible method of treatment.