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[超声造影剂靶向明胶对高淋巴转移小鼠腹水肝癌细胞系摄取的影响]

[Effect of ultrasound contrast agent targeting gelatin on uptake of mouse ascites hepatocellular carcinoma cell lines with high lymphatic metastasis].

作者信息

He Y, Yang L, Yuan J J, Zhu H H, Shao L Y

机构信息

Department of Ultrasound, Henan People's Hospital, Zhengzhou 450000, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2020 Apr 23;42(4):319-324. doi: 10.3760/cma.j.cn112152-20191016-00670.

Abstract

To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion. The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability was evaluated by uptake test, and the imaging effect of the contrast agent was evaluated by developing test. The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect . Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence than those with low expression of gelsolin protein (<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration (<0.05). Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect .

摘要

分析靶向明胶的超声造影剂对小鼠肝癌高淋巴转移细胞系伴腹水摄取的影响。采用改良的复乳溶剂蒸发法构建大分子造影剂聚乳酸-羟基乙酸共聚物-羧基(PLGA-Cooh)。使用碳二亚胺将明胶单克隆抗体与造影剂PLGA-Cooh连接,建立靶向超声造影剂Gsn-PLGA。用激光粒度分析仪测量靶向超声造影剂的粒径和Zeta电位。通过免疫荧光评估造影剂与明胶单克隆抗体的表面结合。将具有高淋巴转移的Hca-F细胞接种于伴有腹水的肝癌小鼠体内。通过摄取试验评估靶向能力,通过显影试验评估造影剂的成像效果。该造影剂为白色粉末,水溶性良好。平均粒径和表面电位分别为(569.68±6.96)nm和(-10.95±2.43)mV。用DiI标记的非靶向和靶向超声造影剂的荧光抗体结合率分别为0.84%和95.89%。结果表明,靶向超声造影剂Gsn-PLGA具有较好的显影效果。凝溶胶蛋白高表达的Hca-F细胞比凝溶胶蛋白低表达的细胞对靶向超声造影剂的摄取能力更强,绿色荧光更强(<0.05)。此外,靶向超声造影剂Gsn-PLGA对凝溶胶蛋白的靶向性更强。靶向超声造影剂Gsn-PLGA的回声均匀、细腻,后方回声无衰减。同时,随着造影剂浓度的增加,显影效果更明显(<0.05)。靶向明胶的超声造影剂Gsn-PLGA能与高表达明胶的Hca-F细胞结合,并显示出良好的成像效果。

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