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开发用于血管外对比增强超声靶向肝细胞癌的纳米级材料的试验。

Trials in developing a nanoscale material for extravascular contrast-enhanced ultrasound targeting hepatocellular carcinoma.

作者信息

Wu Size, Lin Xiyuan

机构信息

Department of Ultrasound, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China.

Department of Emergency Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China.

出版信息

PeerJ. 2020 Dec 7;8:e10403. doi: 10.7717/peerj.10403. eCollection 2020.

DOI:10.7717/peerj.10403
PMID:33354418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7727372/
Abstract

BACKGROUND

Medical imaging is an important approach for the diagnosis of hepatocellular carcinoma (HCC), a common life threaten disease, however, the diagnostic efficiency is still not optimal. Developing a novel method to improve diagnosis is necessary. The aim of this project was to formulate a material that can combine with GPC3 of HCC for targeted enhanced ultrasound.

METHODS

A material of sulfur hexafluoride (SF) filled liposome microbubbles and conjugated with synthesized peptide (LSPMbs) was prepared and assessed in vitro and vivo. Liposome microbubbles were made of DPPC, DPPG, DSPE-PEG2000,and SF, using thin film method to form shell, followed filling SF, and conjugating peptide. A carbodiimide method was used for covalent conjugation of peptide to LSMbs.

RESULTS

The prepared LSPMbs appeared round shaped, with size of 380.9 ±  176.5 nm, and Zeta potential of -51.4 ±  10.4mV. LSPMbs showed high affinity to Huh-7 cells in vitro, presented good enhanced ultrasound effects, did not show cytotoxicity, and did not exhibit targeted fluorescence and enhanced ultrasound in animal xenograft tumors.

CONCLUSION

Extravascular contrast-enhanced ultrasound targeted GPC3 on HCC may not be realized, and the reason may be that targeted contrast agents of microbubbles are hard to access and accumulate in the tumor stroma and matrix.

摘要

背景

医学成像技术是诊断肝细胞癌（HCC）的重要手段，肝细胞癌是一种常见的危及生命的疾病，然而其诊断效率仍不尽人意。开发一种新的方法来改善诊断很有必要。本项目的目的是制备一种能与肝癌细胞中GPC3结合的材料用于靶向增强超声成像。

方法

制备了一种填充六氟化硫（SF）的脂质体微泡并与合成肽偶联的材料（LSPMbs），并在体外和体内进行评估。脂质体微泡由二棕榈酰磷脂酰胆碱（DPPC）、二棕榈酰磷脂酰甘油（DPPG）、二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG2000）和SF制成，采用薄膜法形成外壳，随后填充SF并偶联肽。采用碳二亚胺法将肽共价偶联到LSMbs上。

结果

制备的LSPMbs呈圆形，大小为380.9±176.5nm，Zeta电位为-51.4±10.4mV。LSPMbs在体外对Huh-7细胞表现出高亲和力，呈现出良好的增强超声效果，无细胞毒性，在动物异种移植瘤中未表现出靶向荧光和增强超声效果。

结论

难以实现血管外对比增强超声对肝癌中GPC3的靶向作用，原因可能是微泡靶向造影剂难以进入并积聚在肿瘤基质和间质中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/4e778d52b1f0/peerj-08-10403-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/8e1ad7ad8643/peerj-08-10403-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/98f2a7b015d5/peerj-08-10403-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/829a6c61577e/peerj-08-10403-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/f47e60fc922e/peerj-08-10403-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/60a67ffc8772/peerj-08-10403-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/2d0ef5626a19/peerj-08-10403-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/7a9325c03de5/peerj-08-10403-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/c9bd415092eb/peerj-08-10403-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/31bef92814f4/peerj-08-10403-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/4e778d52b1f0/peerj-08-10403-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/8e1ad7ad8643/peerj-08-10403-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/98f2a7b015d5/peerj-08-10403-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/829a6c61577e/peerj-08-10403-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/f47e60fc922e/peerj-08-10403-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/60a67ffc8772/peerj-08-10403-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/2d0ef5626a19/peerj-08-10403-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/7a9325c03de5/peerj-08-10403-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/c9bd415092eb/peerj-08-10403-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/31bef92814f4/peerj-08-10403-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae5/7727372/4e778d52b1f0/peerj-08-10403-g010.jpg

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