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

Authors Yang H, Jing H, Han X, Tan H, Cheng W

Received 11 December 2020

Accepted for publication 20 January 2021

Published 11 February 2021 Volume 2021:15 Pages 531—542

DOI https://doi.org/10.2147/DDDT.S296880

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


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 China

Correspondence: Wen Cheng
Department of Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China
Tel +86 13313677182
Fax +86 451 85718392
Email hrbchengwen@163.com

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.

Keywords: minimally invasive cancer treatment strategy, sonosensitizer, PI3K/mTOR inhibitor, IR820 nanobubbles

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