Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin

Ultrasonics
Tomohiro OsakiYoshiharu Okamoto

Abstract

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound and a sonosensitizer agent. We examined whether 5-aminolevulinic acid (5-ALA)-based SDT at 1 or 3 MHz could enhance the cytotoxicity of bleomycin (BLM) toward mouse mammary tumor cells both in vitro and in vivo. At 1 MHz, cell viability in the 5-ALA-based SDT group at 1, 2, and 3 W/cm(2) was 34.30%, 50.90%, and 60.16%, respectively. Cell viability in the 5-ALA-based SDT+BLM group at 1, 2, and 3 W/cm(2) was 0.09%, 0.32%, and 0.17%, respectively. In contrast, at 3 MHz, 5-ALA-based SDT+BLM did not show pronounced cytotoxicity. In the in vivo study, 5-ALA-based SDT+BLM was significantly more cytotoxic than 5-ALA-based SDT at 1 MHz and 3 MHz. These findings suggest that the mechanism of tumor shrinkage induced by 5-ALA-based SDT+BLM might involve not only direct cell killing, but also vascular shutdown. Thus, we show here that 5-ALA-based SDT enhances the efficacy of BLM both in vitro and in vivo.

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Citations

Apr 1, 2017·Therapeutic Delivery·Henry Hirschberg, Steen J Madsen
Mar 28, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tomohiro OsakiYoshiharu Okamoto
Jul 23, 2016·Journal of Biomedical Optics·Jonathan GonzalesHenry Hirschberg
Oct 20, 2018·Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine·Maxime LafondShin-Ichiro Umemura

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