We previously developed novel liposomal nanobubbles (Bubble
liposomes [BL]) that oscillate and collapse in an ultrasound field, generating heat and
shock waves. We aimed to investigate the feasibility of
cancer therapy using the combination of BL and ultrasound. In addition, we investigated the anti-
tumor mechanism of this
cancer therapy. Colon-26 cells were inoculated into the flank of BALB/c mice to induce
tumors. After 8 days, BL or saline was intratumorally injected, followed by transdermal ultrasound exposure of
tumor tissue (1 MHz, 0-4 W/cm2 , 2 min). The anti-
tumor effects were evaluated by histology (
necrosis) and
tumor growth. In vivo cell depletion assays were performed to identify the immune cells responsible for anti-
tumor effects.
Tumor temperatures were significantly higher when treated with BL + ultrasound than ultrasound alone. Intratumoral BL caused extensive tissue
necrosis at 3-4 W/cm2 of ultrasound exposure. In addition, BL + ultrasound significantly suppressed
tumor growth at 2-4 W/cm2 . In vivo depletion of CD8+ T cells (not NK or CD4+ T cells) completely blocked the effect of BL + ultrasound on
tumor growth. These data suggest that CD8+ T cells play a critical role in
tumor growth suppression. Finally, we concluded that BL + ultrasound, which can prime the anti-
tumor cellular immune system, may be an effective
hyperthermia strategy for
cancer treatment.