Synergistic Anticancer Strategy of Sonodynamic Therapy Combined with PI-103 Against Hepatocellular Carcinoma

PURPOSE: Sonodynamic therapy (SDT) is considered a promising therapeutic strategy for the effective elimination of cancer cells. However, developing novel sonosensitizers with potentially high SDT efficacy remains a considerable challenge. Herein, we utilized near-infrared dye IR820 nanobubbles (NBs) combined with a dual PI3K/mTOR inhibitor PI-103 for the SDT treatment of hepatocellular carcinoma (HCC) in vitro. METHODS: The generated reactive oxygen species (ROS) were quantified using 2,7-dichlorodihydrofluorescein diacetate to determine the feasibility of using IR820 NBs as a potential sonosensitizer. The inhibition effects of the synergistic therapy was examined using the cell counting Kit 8 assay and apoptosis assay. JC-1 staining was performed to study mitochondrial membrane depolarization, and the transwell assay was used for cell migration analysis. RESULTS: The particle size and zeta potential of IR820 NBs were 545.5±93.1 nm and −5.19±1.73 mV, respectively. ROS accumulation was observed after HepG2 cells were treated with IR820 NBs under ultrasound irradiation. The SDT combined with PI-103 group inhibited cell viability and migration more strongly than the other groups (P < 0.01). The apoptosis assay also demonstrated a relatively high anti-HCC efficacy with the synergistic therapy, while JC-1 staining showed a decrease in the mitochondrial membrane potential after the combined treatment. CONCLUSION: The combination of SDT and PI-103 was very effective in suppressing HCC proliferation, which might help develop new minimally invasive cancer treatment strategies.