安徽医科大学学报2024，Vol.59Issue(12)：2087-2094,8.DOI:10.19405/j.cnki.issn1000-1492.2024.12.004
成纤维细胞激活蛋白诱导胞内自组装Gd-纳米粒子对比剂的合成及MR成像研究
Synthesis of fibroblast activation protein-induced intracellular self-assembly Gd-nanoparticle contrast agent and study of MR imaging
摘要
Abstract
Objective To synthesis a Gd-labeled molecular probe capable of responding to fibroblast activation pro-tein(FAP)highly expressed in tumor-associated fibroblasts for magnetic resonance imaging studies of pancreatic cancer.Methods The chemical structure of Z-Gly-Pro-Cys-Lys(Gd-DOTA)-CBT(contrast agent 1)was charac-terized through mass spectrometry analysis.High-performance liquid chromatography(HPLC)was used to verify the contrast agent 1 formed a dimer under the cleavage of fibroblast activation protease(FAP)in vitro,and further self-assembled to form Gd-nanoparticles.The cell counting Kit-8(CCK-8)assay was used for biological safety a-nalysis.BxPc-3 tumor-bearing mice were established and randomly divided into three groups,3 mice intravenously(i.v.)injected with 0.08 mmol/kg contrast agent 1 through tail vein were designated as the experimental group,3 mice i.v.injected with 0.08 mmol/kg Gd-DTPA were designated as the control group,and 3 mice i.v.injected with normal saline were designated as the blank control group(n=3).Dynamic MR scanning from 0 to 3 hours was performed for them,respectively.The enhancement effects of T1-and T2-weighted imaging were observed and the rate of change in the tumor-to-muscle ratio(T/M)over time was analyzed.Results Contrast agent 1 efficient-ly responded to FAP in vitro,forming dimers under the action of FAP,and further self-assembled to form nanoparti-cle structures.Contrast agent 1 has good biocompatibility.The BxPc-3 tumor-bearing mice showed that the T1-weighted contrast of the tumor reached its highest level at 2 h post injection of contrast agent 1 or Gd-DTPA.In T1-weighted imaging,the T/M at 2 h in the experimental group was 135.20％±0.06％of 0 h,the T/M at 2 h in the Gd-DTPA group was 115.70％±0.05％of 0 h and the T/M at 2 h in the saline group was 113.5％±0.02％of 0 h.Compared with Gd-DTPA control group,the experimental group had significantly enhanced T1-weighted MR contrast,and the difference was statistically significant(P＜0.01).In tumor T2-weighted imaging,the T/M quan-titative analysis showed that the tumor T2-weighted contrast enhancement of the three groups was relatively small,and the T/M of the experimental group and the control group at 0.5 h was 94.60±0.03％and 106.30±0.04％of the 0 h,respectively.In the normal saline group,T/M at 0.5 h was 102.20±0.002％of that at 0 h,and no sig-nificant enhancement of the T2-weighted MR contrast of tumor was observed.Conclusion Successfully construct a FAP-responsive molecular probe which can self-assemble to form a Gd-nanoparticle structure in tumor cells under the cleavage of FAP,effectively improving the enrichment of Gd in the target region,and enhancing T1-weighted magnetic resonance imaging of pancreatic cancer,which has potential clinical application value.关键词
对比剂/点击反应/自组装/成纤维细胞激活蛋白/胰腺癌/T1加权成像Key words
contrast agent/click reaction/self-assembly/fibroblast activation protein/pancreatic cancer/T1 weighted magnetic resonance imaging分类
医药卫生引用本文复制引用
郭祥源,郑一凡,张曼琳,任怡博,蒋金辉..成纤维细胞激活蛋白诱导胞内自组装Gd-纳米粒子对比剂的合成及MR成像研究[J].安徽医科大学学报,2024,59(12):2087-2094,8.基金项目
安徽省卫生健康科研项目(编号:AHWJ2023A20105) Health Research Project of Anhui Province(No.AHWJ2023A20105) （编号:AHWJ2023A20105）
