Open AccessTumor growth suppression by the combination of nanobubbles and ultrasound
Author(s) -
Suzuki Ryo,
Oda Yusuke,
Omata Daiki,
Nishiie Norihito,
Koshima Risa,
Shiono Yasuyuki,
Sawaguchi Yoshikazu,
Unga Johan,
Naoi Tomoyuki,
Negishi Yoichi,
Kawakami Shigeru,
Hashida Mitsuru,
Maruyama Kazuo
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12867
Subject(s) - in vivo , ultrasound , cancer research , hyperthermia , immune system , medicine , necrosis , cancer , pathology , chemistry , immunology , biology , radiology , microbiology and biotechnology
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.