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


中文翻译：

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声动力疗法联合PI-103抗肝细胞癌的协同抗癌策略

目的：声动力疗法（SDT）被认为是一种有效消除癌细胞的有前途的治疗策略。然而，开发具有潜在高 SDT 功效的新型声敏剂仍然是一个相当大的挑战。在此，我们利用近红外染料 IR820 纳米气泡 (NBs) 与双 PI3K/mTOR 抑制剂 PI-103 联合用于体外 SDT 治疗肝细胞癌 (HCC)。
方法：使用 2,7-二氯二氢荧光素二乙酸酯对产生的活性氧 (ROS) 进行量化，以确定使用 IR820 NB 作为潜在声敏剂的可行性。使用细胞计数试剂盒8测定法和细胞凋亡测定法检查协同治疗的抑制作用。进行JC-1染色以研究线粒体膜去极化，并使用transwell测定法进行细胞迁移分析。
结果：IR820 NB 的粒径和 zeta 电位分别为 545.5± 93.1 nm 和 - 5.19± 1.73 mV。在超声照射下用 IR820 NB 处理 HepG2 细胞后观察到 ROS 积累。SDT联合PI-103组比其他组更强烈地抑制细胞活力和迁移（P <0.01）。细胞凋亡测定还证明了协同治疗具有相对较高的抗 HCC 功效，而 JC-1 染色显示联合治疗后线粒体膜电位降低。
结论： SDT与PI-103联合应用对抑制HCC增殖非常有效，可能有助于开发新的微创癌症治疗策略。

关键词：微创癌症治疗策略、声敏剂、PI3K/mTOR 抑制剂、IR820 纳米气泡