Sinoporphyrin sodium mediated sonodynamic therapy generates superoxide anion under hypoxia environment

Sonodynamic therapy (SDT), which employs the interaction between low-intensity ultrasound and a non-toxic sonosensitizer to produce various reactive oxygen species (ROS), offers the possibility of treating cancer non-invasively. In this work, systematic experiments were conducted to detect the types of ROS produced in the process of sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT). We found that the fluorescence intensity of the superoxide anion (˙O2−) specific probe BES-SO in the DVDMS-SDT group was significantly higher than that in the ultrasound group alone, while it decreased with the introduction of superoxide dismutase (˙O2− scavenger), indicating the production of ˙O2−. At the same molality concentration, DVDMS is superior to protoporphyrin IX (PpIX) and hematoporphyrin monomethyl ether (HMME) in ˙O2− generation, indicating that the properties of sonosensitizers determine the ˙O2− yield. Although ultrasound alone could also produce ˙O2− by pyrolyzing water, the significance of DVMDS lies in reducing the ultrasonic intensity threshold and improving the low efficiency of pure ultrasound in producing ˙O2−. More importantly, DVDMS-SDT is involved in the process of ˙O2− even at low levels of oxygenation, showing its greater superiority for the treatment of tumors under a hypoxic environment.