Sonodynamic Therapy on Intracranial Glioblastoma Xenografts Using Sinoporphyrin Sodium Delivered by Ultrasound with Microbubbles

—Sonodynamic therapy (SDT) is a promising nonin- vasive method for cancer treatment. The anti-tumor effect of sinoporphyrin sodium(DVDMS)-mediated SDTon nude mice bearing intracranial U87 MG-Red-FLuc human glioblastoma was investigated.Focusedultrasound(FUS) withmicrobubbles (MBs) was utilized to open the blood-brain barrier for enhanc- ing the delivery of the sonosensitizer DVDMS to the brain tumor first, and then the SDT treatment was performed. The in vitro study showed obvious cytotoxicity of DVDMS-medi- ated SDT (center frequency: 0.996 MHz, acoustic power: 1.7 W, pulse repletion frequency: 1 Hz, duty cycle: 30%, duration: 1 min) on U87 MG-Red-FLuc cells. The results indicated that more DVDMS accumulation in the tumor sites was induced by FUS with MBs by 3.43 folds of unsonicated ones.Longitudinal bioluminescenceimagingillustrated that the intracranial glioblastoma progression in nude mice treated with SDT was retarded compared to the untreated group. The median survival time was prolonged to 30.25 days after SDT treatment by 27.37%. The anti-proliferation effect and cell apoptosis induction was further confirmed by immunohisto- chemical examinations.These resultsof the study suggestedthat SDT using the sonosensitizer DVDMS delivered by FUS with MBsmay provide a newpromising therapeutic strategy against glioblastoma.