Department of Ultrasound, Harbin Medical University Cancer Hospital , Harbin , China.
Drug Deliv. 2019 Dec;26(1):944-951. doi: 10.1080/10717544.2019.1667450.
This study aimed at investigating the tumor stiffness of hepatocellular carcinoma (HCC) bearing mice model in vivo to evaluate the therapeutic efficacy of targeting nanobubbles (TNBS) conjugated with NET-1 siRNA (NET-1 siRNA-TNBS). Also tested whether shear wave elastography (SWE) could demonstrate the pathological tumor changes and used to monitor therapeutic efficacy as a noninvasive method. The HCC bearing mice model was established by injecting human HCC cell line (HepG2). The mice were then divided into three groups randomly, and were treated with TNBS conjugated with NET-1 siRNA, TNBS conjugated with negative control gene, and saline as control. US-SWE was performed for three times. SWE values of all the tumors in three groups were increased with tumor growth. Emax was correlated with tumor size ( < .05). NET-1 gene (treatment group) significantly delayed the growth of tumor size compared to other two groups ( < .0001), showing a significantly increased Emax ( < .05). Immunohistochemical results showed that the NET-1 protein expression was significantly lower than the negative control and blank groups. In conclusion, TNBS conjugated with NET-1 siRNA inhibited tumor growth and prolonged the life of experimental animals. SWE provided a noninvasive and real time imaging method to detect the changes in tumor development.
本研究旨在通过体内实验研究荷肝癌（HCC）小鼠模型的肿瘤硬度，以评估靶向纳米泡（NET-1 siRNA 结合的 TNBS）的治疗效果。同时，也研究了剪切波弹性成像（SWE）是否可以显示肿瘤的病理变化，并作为一种非侵入性方法用于监测治疗效果。通过注射人肝癌细胞系（HepG2）建立 HCC 荷瘤小鼠模型。然后，将小鼠随机分为三组，分别接受 NET-1 siRNA 结合的 TNBS、NET-1 阴性对照基因结合的 TNBS 和生理盐水作为对照治疗。对三组所有肿瘤进行三次 US-SWE 检测。随着肿瘤生长，三组所有肿瘤的 SWE 值均升高，Emax 与肿瘤大小呈正相关（ < .05）。与其他两组相比，NET-1 基因（治疗组）显著延缓了肿瘤生长（ < .0001），表现出明显更高的 Emax（ < .05）。免疫组织化学结果显示，NET-1 蛋白表达明显低于阴性对照组和空白对照组。总之，NET-1 siRNA 结合的 TNBS 抑制肿瘤生长，延长了实验动物的寿命。SWE 提供了一种非侵入性、实时的成像方法，用于检测肿瘤发展的变化。
