Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, 150081, People's Republic of China.
Drug Des Devel Ther. 2021 Feb 11;15:531-542. doi: 10.2147/DDDT.S296880. eCollection 2021.
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.
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.
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.
The combination of SDT and PI-103 was very effective in suppressing HCC proliferation, which might help develop new minimally invasive cancer treatment strategies.
声动力学疗法（SDT）被认为是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 疗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 纳米泡（NBs）结合双 PI3K/mTOR 抑制剂 PI-103 进行体外肝癌（HCC）的 SDT 治疗。
使用 2,7-二氯二氢荧光素二乙酸酯来量化产生的活性氧（ROS），以确定将 IR820 NBs 用作潜在声敏剂的可行性。使用细胞计数试剂盒 8 测定法和凋亡测定法来检查协同治疗的抑制效果。进行 JC-1 染色以研究线粒体膜去极化，并用 Transwell 测定法进行细胞迁移分析。
IR820 NBs 的粒径和 zeta 电位分别为 545.5±93.1nm 和-5.19±1.73mV。在超声辐照下用 HepG2 细胞处理 IR820 NBs 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）。凋亡测定也显示协同治疗具有相对较高的抗 HCC 疗效，而 JC-1 染色显示联合治疗后线粒体膜电位降低。
SDT 与 PI-103 的联合非常有效地抑制 HCC 的增殖，这可能有助于开发新的微创癌症治疗策略。
