| 摘要: |
| 目的:制备一种包裹液态氟碳，载肝癌治疗基因质粒，并具有叶酸分子靶向性的纳米级超声分子探针, 研究其基本特性及超声显像能力?
方法:通过聚乙二醇亚胺在PLGA表面连接叶酸（Fa）分子，制成靶向膜材料(PLGA-Fa)后,采用双乳化法制备载有PFP的纳米级靶向超声造影剂，将其与多聚赖氨酸孵育后，形成表面带正电荷的阳离子，利用正负电荷吸附作用，使纳米粒表面载上质粒C（PLGA-Fa-PFP-C）。 分别用加热及LIFU辐照的方式处理纳米粒，于显微镜下观察其相变情况，于超声造影模式下观察其体外显影效果。另同样用双乳法制备无叶酸的非靶向造影剂，将两者分别与肝癌细胞HepG2孵育，观察其寻靶能力。
结果: 成功制备了载有质粒、PFP的纳米级靶向超声造影剂(Fa-PLGA/PFP/C)，该纳米微粒大小均匀,形态圆整,分散性好，直径分布为200.5nm，平均电位为+37MV,当加热至50度时及用LIFU5档辐照后5分钟后，显微镜下可见较多的纳米粒相变，超声造影模式下亦可见显像;并在细胞实验中观察到该靶向造影剂有明显的靶向作用。
结论:本研究成功制备了一种载质粒及PFP的纳米级靶向超声造影剂(Fa-PLGA/PFP/C)，该纳米粒可用于超声造影显像，并具有肿瘤靶向性。 |
| 关键词: 叶酸 靶向 质粒；超声； |
| DOI： |
| 投稿时间：2020-03-17修订日期：2020-03-27 |
| 基金项目:国家自然科学基金(81760317、81871365)；海南省自然科学基金(818MS126)；海南省重点研发计划(ZDYF2019136) |
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| Preparation of targeted ultrasound molecular probe carrying suicide gene and experimental research of its ultrasound imaging capability |
| yangdayan,chenqiqing,zhongtingting,zhangmin,chenyan,xielin,wangminghua,jingxiangxiang |
| () |
| Abstract: |
| Objective: To prepare a Wrapped liquid fluorocarbon, which can carry liver cancer therapeutic genes and has folic acid molecular targeting nano-scale ultrasound molecular probe, and to study its basic characteristics and ultrasound imaging capability.
Methods: Pegylated imine was used to connect folic acid (Fa) molecules on the surface of PLGA to prepare targeted membrane material (PLGA-Fa), then PFP-loaded nano-scale targeted ultrasound contrast agent was prepared by double emulsification method, and after incubation with polylysine, positively charged cations were formed on the surface, and plasmids (PLGA-Fa-PFP-S) were loaded on the surface of nanoparticles by positive and negative charge adsorption. The nanoparticles were treated by heating and LIFU irradiation respectively. The phase change was observed under a microscope and the Image display effect in vitro was observed in contrast-enhanced ultrasound mode. Results: Nanoscale targeted ultrasound contrast agent (Fa-PLGA/PFP/S) loaded with plasmid and PFP was successfully prepared. The nanoparticles were uniform in size, round in shape, good in dispersibility, with a diameter distribution of 200.5nm and an average potential of +37MV. When heated to 50 degrees and irradiated with LIFU 5th stage radiation for 5 minutes, more nanoparticle phase changes were visible under the microscope, and imaging was also visible under ultrasound contrast mode.In addition, folate - free non-targeted contrast agents were prepared by double - emulsion method，they were incubated with liver cancer cells HepG2 respectively to observe their target-seeking ability.
Conclusion: A nano-scale targeted ultrasound contrast agent (Fa-PLGA/PFP/S) with plasmid and PFP was successfully prepared in this study. The nanoparticles can be used for ultrasound contrast imaging.It was also observed that the targeted contrast agent has obvious targeting effect in cell experiments. |
| Key words: folic acid target plasmid ultrasound |
