Abstract
Intravesical instillation of chemotherapy has been performed to reduce the risk of intravesical recurrence of bladder cancer. However, its antitumor effect is not necessarily sufficient, which may be partially due to inadequate delivery of intravesically administered chemotherapeutic agents to bladder tumors. Ultrasound irradiation to target tissues in the presence of microbubbles is a technique to transiently enhance cell membrane permeability and achieve efficient drug delivery to the desired sites without damage to non-target areas; this technique has been used in chemotherapy, immunotherapy, gene therapy, and radiotherapy for the treatment of various cancers. However, the effectiveness of combining intravesical instillation of chemotherapy and this strategy for the treatment of bladder cancer has not been fully investigated. This report shows that mitomycin C combined with ultrasound and microbubbles has a higher antitumor effect than mitomycin C alone against mouse bladder cancer cells. Next, the antitumor effect of intravesical instillation of chemotherapy combined with ultrasound and microbubbles was demonstrated using an orthotopic mouse bladder cancer model. In vivo experiments showed that ultrasound irradiation in the presence of microbubbles enhanced the local delivery of fluorescent molecules and had the potential to enhance the antitumor effect of intravesical instillation of chemotherapy without visible damage to the surrounding normal tissues. The results of the present study demonstrate that intravesical chemotherapy combined with ultrasound and microbubbles is potentially a safe and effective treatment for bladder cancer.