Yang Huajing, Qu Yunfeng, Tian Yuhang, Wang Chunyue, Sun Yucao, Dai Zhifei, Yue Xiuli, Cheng Wen
Department of Ultrasound, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang Province 150081, China.
Department of Biomedical Engineering, College of Future Technology, National Biomedical Imaging Center, Peking University, No.5 Yiheyuan Road, Beijing 100871, China.
ACS Omega. 2024 Dec 18;9(52):51253-51263. doi: 10.1021/acsomega.4c07746. eCollection 2024 Dec 31.
: To assess the anticancer effect of microbubbles (MBs) in combination with sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy (SDT) for the in vitro and in vivo treatment of hepatocellular carcinoma (HCC). : HepG2 cells were used for in vitro experiments. Reactive oxygen species (ROS) production was detected using 2',7'-dichlorodihydrofluorescein diacetate and singlet oxygen sensor green in vitro and in solution, respectively. Cytotoxicity was evaluated using a Cell Counting Kit 8 assay and the calcein AM/PI double-staining method. Annexin V-FITC/PI staining was employed to analyze the rate of cell apoptosis. Cell surface calreticulin exposure, high mobility group box 1 release, and adenosine triphosphate secretion were measured to detect immunogenic cell death (ICD). The anticancer effect of the combination therapy was further assessed in Hepa1-6 tumor-bearing mice. : Compared with SDT alone, ROS production in the MBs + SDT group was enhanced 1.2-fold ( < 0.0001). The cytotoxic effect of DVDMS-mediated SDT on HepG2 cells was concentration-dependent, and the additional application of MBs increased cytotoxicity. Additionally, MBs augmented the SDT-induced apoptosis rate from 33.26 ± 13.48 to 72.95 ± 7.95% ( < 0.01). Notably, our results demonstrated that MBs can enhance SDT-induced ICD. In in vivo experiments, SDT combined with MBs significantly reduced tumor volume, with negligible differences in mouse body weight. Furthermore, MBs effectively enhanced SDT-induced tumor tissue destruction. : The present study indicates that MBs can markedly improve the anticancer effects of SDT in HCC.
评估微泡（MBs）联合血卟啉单甲醚（DVDMS）介导的声动力疗法（SDT）对肝细胞癌（HCC）进行体外和体内治疗的抗癌效果。：采用HepG2细胞进行体外实验。分别使用2',7'-二氯二氢荧光素二乙酸酯和单态氧传感器绿在体外和溶液中检测活性氧（ROS）的产生。使用细胞计数试剂盒8检测法和钙黄绿素AM/PI双染色法评估细胞毒性。采用膜联蛋白V-FITC/PI染色分析细胞凋亡率。测量细胞表面钙网蛋白暴露、高迁移率族蛋白B1释放和三磷酸腺苷分泌以检测免疫原性细胞死亡（ICD）。在荷Hepa1-6肿瘤小鼠中进一步评估联合治疗的抗癌效果。：与单独的SDT相比，MBs+SDT组的ROS产生增加了1.2倍（<0.0001）。DVDMS介导的SDT对HepG2细胞的细胞毒性作用呈浓度依赖性，额外应用MBs增加了细胞毒性。此外，MBs将SDT诱导的凋亡率从33.26±13.48%提高到72.95±7.95%（<0.01）。值得注意的是，我们的结果表明MBs可以增强SDT诱导的ICD。在体内实验中，SDT联合MBs显著减小了肿瘤体积，小鼠体重差异可忽略不计。此外，MBs有效增强了SDT诱导的肿瘤组织破坏。：本研究表明MBs可显著提高SDT对HCC的抗癌效果。
