Drug Design, Development and Therapy (Feb 2021)
Synergistic Anticancer Strategy of Sonodynamic Therapy Combined with PI-103 Against Hepatocellular Carcinoma
Abstract
Huajing Yang, Hui Jing, Xue Han, Haoyan Tan, Wen Cheng Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, 150081, People’s Republic of ChinaCorrespondence: Wen ChengDepartment of Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of ChinaTel +86 13313677182Fax +86 451 85718392Email [email protected]: 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.Keywords: minimally invasive cancer treatment strategy, sonosensitizer, PI3K/mTOR inhibitor, IR820 nanobubbles
