OPEN Cancer science | 29 Dec 2015
R Suzuki, Y Oda, D Omata, N Nishiie, R Koshima, Y Shiono, Y Sawaguchi, J Unga, T Naoi, Y Negishi, S Kawakami, M Hashida and K Maruyama
We previously developed novel liposomal nanobubbles (Bubble liposomes; BLs) that oscillate and collapse in an ultrasound field, generating heat and shock waves. We aimed to investigate the feasibility of cancer therapy by the combination of BLs and ultrasound (BLs + 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, BLs or saline was intratumorally injected, followed by transdermal ultrasound exposure of tumor tissue (1 MHz, 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 BLs + ultrasound than ultrasound alone. Intratumoral BLs caused extensive tissue necrosis at 3-4 W/cm(2) of ultrasound exposure. In addition, BLs + ultrasound significantly suppressed tumor growth at 2-4 W/cm(2) . In vivo depletion of CD8(+) T cells (not NK or CD4(+) T cells) completely blocked the effect of BLs + ultrasound on tumor growth. These data suggest that CD8(+) T cells play a critical role in tumor growth suppression. Finally, we concluded that BLs + ultrasound which can prime the anti-tumor cellular immune system may be an effective hyperthermia strategy for cancer treatment. This article is protected by copyright. All rights reserved.
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