Abstract
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.
Acknowledgments
The human HCC cell line HepG2 was obtained from the Institute of Cancer Research affiliated with the Harbin Medical University and approved by Ethics Committee of Harbin Medical University.
Author Contributions
Methodology, H.Y.; validation, H.Y., H.T.; data curation, X.H.; writing—original draft preparation, H.Y.; writing—review and editing, W.C.; supervision, H.J.; project administration, W.C.; funding acquisition, W.C and H.J. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.