Irradiation with ultrasound of low output intensity increased chemosensitivity of subcutaneous solid tumors to an anti-cancer agent

Ultrasound is a possible mechanical method to deliver small molecules into target cells. In order to evaluate the therapeutic potentials provided by ultrasound irradiation, we compared anti-tumor effects of electroporation- and ultrasound-mediated chemotherapy and efficacy of gene transfer by the two methods. Electric pulses (5 Hz, 100 V/cm, 8 square-wave/100 μsec) or ultrasound (1 MHz, 2 W/cm2, 5 min) was delivered to subcutaneous solid tumors of murine lymphoma after the tumor-bearing mice received an intraperitoneal injection of bleomycin (BLM) (2.5 mg) or intratumoral injection of plasmid DNA containing the luciferase reporter gene. Administration of BLM alone did not affect the subsequent tumor growth but additive treatment with ultrasound irradiation suppressed the growth to the same level as electroporation. The luciferase activity of the DNA-injected tumors showed that ultrasound irradiation achieved better transfection efficiency than plasmid DNA injection alone but the efficacy was not as great as that by electroporation. The low energy level of ultrasound that is currently used for a diagnostic purpose and physical therapy in clinical fields can thereby increase the in vivo chemosensitivity of treated tumors but further modifications are necessary to achieve better efficacy of the ultrasound-mediated gene transfer.