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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  MH z, 0–4 W/cm 2 , 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/cm 2  of ultrasound exposure. In addition,  BL  + ultrasound significantly suppressed tumor growth at 2–4 W/cm 2 .  In vivo  depletion of  CD 8 +  T cells (not  NK  or  CD 4 +  T cells) completely blocked the effect of  BL  + ultrasound on tumor growth. These data suggest that  CD 8 +  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.

Tumor growth suppression by the combination of nanobubbles and ultrasound