Tumor growth suppression by the combination of nanobubbles and ultrasound.

Abstract

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.

• Authors: Ryo Suzuki, Yusuke Oda, Daiki Omata, Norihito Nishiie, Risa Koshima, Yasuyuki Shiono, Yoshikazu Sawaguchi, Johan Unga, Tomoyuki Naoi, Yoichi Negishi, Shigeru Kawakami, Mitsuru Hashida, Kazuo Maruyama
• Journal: Cancer science (Cancer Sci) Vol. 107 Issue 3 Pg. 217-23 (Mar 2016) ISSN: 1349-7006 [Electronic] England
• PMID: 26707839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Liposomes

Topics

• Animals
• Cell Line, Tumor
• Female
• Hyperthermia, Induced
• Immunity, Cellular
• Liposomes
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (therapeutic use)
• Neoplasm Transplantation
• Neoplasms (immunology, pathology, therapy)
• T-Lymphocytes (immunology)
• Tumor Burden
• Ultrasonic Waves