[1]李贵平,符珍敏,江英,等.肺癌靶向多肽荧光分子探针的研制及其应用[J].中国医学物理学杂志,2020,37(6):762-768.[doi:DOI:10.3969/j.issn.1005-202X.2020.06.020]
　LI Guiping,FU Zhenmin,JIANG Ying,et al.Preparation of polypeptide-based fluorescent molecular probe for targeting lung adenocarcinoma and its application[J].Chinese Journal of Medical Physics,2020,37(6):762-768.[doi:DOI:10.3969/j.issn.1005-202X.2020.06.020]
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肺癌靶向多肽荧光分子探针的研制及其应用()
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《中国医学物理学杂志》[ISSN:1005-202X/CN:44-1351/R]

卷:
37
期数:
2020年第6期
页码:
762-768
栏目:
医学生物物理
出版日期:
2020-06-25

文章信息/Info

Title:
Preparation of polypeptide-based fluorescent molecular probe for targeting lung adenocarcinoma and its application
文章编号:
1005-202X（2020）06-0762-07
作者:
李贵平; 符珍敏; 江英; 齐永帅; 池晓华; 何云
南方医科大学南方医院核医学科， 广东 广州 510515
Author(s):
LI Guiping;  FU Zhenmin;  JIANG Ying;  QI Yongshuai;  CHI Xiaohua;  HE Yun
Department of Nuclear Medicine, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China
关键词:
肺癌; 小分子多肽; 荧光分子探针; A549细胞; 荷瘤裸鼠
Keywords:
Keywords: Lung cancer small molecule polypeptide fluorescent molecular probe A549 cell tumor-bearing nude mice
分类号:
R34；R730.49
DOI:
DOI:10.3969/j.issn.1005-202X.2020.06.020
文献标志码:
A
摘要:
目的：选择能与整合素α3受体结合的小分子多肽cNGQGEQc-L作为靶向载体，将羧基荧光素（FAM）与cNGQGEQc-L连接构建荧光分子探针，通过荧光成像探讨荧光多肽分子探针用于肺腺癌显像的可行性。方法：利用倒置荧光显微镜观察FAM-cNGQGEQc-L与肺腺癌A549细胞结合部位，流式细胞仪检测荧光多肽与A549细胞的竞争抑制实验，观察FAM-cNGQGEQc-L随浓度的增加与肺腺癌A549细胞结合能力的变化情况。通过小动物活体成像仪，观察荧光多肽在荷瘤裸鼠体内的生物分布特点。结果：倒置荧光显微镜显示荧光多肽cNGQGEQc-L能与A549细胞结合，结合部位在细胞膜和细胞质中。流式细胞仪测试结果证明荧光多肽与A549细胞的结合具有特异性和饱和性，当FAM-cNGQGEQc-L浓度为0.125 mmol/L时，荧光多肽与A549细胞的结合趋近饱和。荷瘤裸鼠活体成像显示移植瘤能够摄取荧光多肽，且荧光多肽通过泌尿系统和胆道系统排泄。结论：体外、体内荧光实验结果显示，荧光多肽分子探针FAM-cNGQGEQc-L可与肺腺癌A549细胞、肺癌移植瘤结合，能够特异性靶向肺腺癌。
Abstract:
Abstract: Objective To explore the feasibility of realizing fluorescence imaging of lung adenocarcinoma by polypeptide-based fluorescent molecular probe which is constructed by choosing the small molecule polypeptide cNGQGEQc-L binding to integrin α3 receptor as a targeting carrier, and then connecting fluorescein FAM with cNGQGEQc-L. Methods The combination of FAM-cNGQGEQc-L with lung adenocarcinoma A549 cells was observed by an inverted fluorescence microscope. Flow cytometry was used to detect the competitive inhibition between fluorescence-labeled polypeptide and A549 cells. The change of the binding capacity of FAM-cNGQGEQc-L with A549 cells was also observed as the increasing of FAM-cNGQGEQc-L concentration. The biodistribution characteristics of fluorescence-labeled polypeptide in tumor-bearing nude mice were observed by in vivo small animal imaging. Results The inverted fluorescence microscope showed that FAM-cNGQGEQc-L could bind to A549 cells on the cell membrane and in cytoplasm. The observation by flow cytometry showed that the binding of the fluorescence-labeled polypeptide to A549 cells was characterized by specificity and saturability, and the binding could approach saturation when FAM-cNGQGEQc-L was at the concentration of 0.125 mmol/L. The in vivo imaging of tumor-bearing nude mice showed that fluorescence-labeled polypeptides could be taken up by xenograft tumors and excreted through the urinary system and the biliary system. Conclusion The results of in vitro and in vivo fluorescence experiments demonstrate that the polypeptide-based fluorescent molecular probe FAM-cNGQGEQc-L can not only bind to A549 cells and lung cancer xenograft tumors, but also specifically target lung adenocarcinoma.

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备注/Memo

备注/Memo:
【收稿日期】2020-04-18 【基金项目】广州市科技计划项目（201607010230）；南方医院院长基金（2019Z027，2018C033） 【作者简介】李贵平，博士，主任医师，硕士生导师，研究方向：肿瘤核医学、分子影像学及放射性药物，E-mail: Ligp@smu.edu.cn
更新日期/Last Update: 2020-07-03