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

Ultrasonics. 2016 Apr;67:76-84. doi: 10.1016/j.ultras.2016.01.003. Epub 2016 Jan 12.


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.

Keywords: 5-Aminolevulinic acid; Bleomycin; Sonodynamic therapy; Ultrasound.

MeSH terms

  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / therapeutic use*
  • Animals
  • Bleomycin / administration & dosage
  • Bleomycin / therapeutic use*
  • Cell Survival / drug effects
  • Cytotoxins / administration & dosage
  • Cytotoxins / therapeutic use*
  • In Vitro Techniques
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Ultrasonic Therapy / methods*


  • Cytotoxins
  • Bleomycin
  • Aminolevulinic Acid