γ-Glutamyltranspeptidase-Triggered Intracellular Gadolinium Nanoparticle Formation Enhances the T2-Weighted MR Contrast of Tumor
γ-Glutamyltranspeptidase-Triggered Intracellular Gadolinium Nanoparticle Formation Enhances the T2-Weighted MR Contrast of Tumor
复制标题
γ-谷氨酰转肽酶触发细胞内钆纳米颗粒形成增强肿瘤的 T-2 加权 MR 对比度
DOI：
10.1021/acs.nanolett.8b05154
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发表时间：
2019-04-01
期刊：
影响因子：
10.8
通讯作者：
Liang, Gaolin
中科院分区：
文献类型：
--
作者：
Hai, Zijuan;Ni, Yanhan;Liang, Gaolin
磁共振成像(MRI)在深部内癌的诊断中具有优势，但始终需要造影剂(CA)来提高MRI的敏感性。Gd基试剂在临床上常被用作T-1为主的CA，但利用细胞内形成的Gd纳米粒子在强磁场下增强体内肿瘤的T-2加权MRI尚未见报道。在这里，我们合理地设计了一种基于Gd的探针Glu-Cys(StBu)-Lys(DOTA-Gd)-CBT(1)，它经历了γ-谷氨酰转肽酶(GGT)的切割和胞内CBT-Cys的缩合反应，形成了Gd纳米颗粒(即，活细胞实验表明，1处理的HeLa细胞的r(2)值为27.8 mm(-1)，S(-1)为1，r(2)/r(1)为10.6。荷瘤小鼠的MR成像显示，静脉注射1，2.5h后，肿瘤的T-2MR对比度提高了28.6%。我们预计，当临床上有强大的磁场时，我们的探针1可以用于GGT相关肿瘤的T2加权MRI诊断。
Magnetic resonance imaging (MRI) is advantageous in the diagnosis of deep internal cancers, but contrast agents (CAs) are always needed to improve MRI sensitivity. Gadolinium (Gd)-based agents are routinely used as T-1-dominated CAs in clinic but using intracellularly formed Gd nanoparticles to enhance the T-2-weighted MRI of tumor in vivo at high magnetic field has not been reported. Herein, we rationally designed a "smart" Gd-based probe Glu-Cys(StBu)-Lys(DOTA-Gd)-CBT (1), which was subjected to gamma-glutamyltranspeptidase (GGT) cleavage and an intracellular CBT-Cys condensation reaction to form Gd nanoparticles (i.e., 1-NPs) to enhance the T-2-weighted MR contrast of tumor in vivo at 9.4 T. Living cell experiments indicated that the 1-treated HeLa cells had an r(2) value of 27.8 mM(-1) s(-1) and an r(2)/r(1) ratio of 10.6. MR imaging of HeLa tumor-bearing mice indicated that the T-2 MR contrast of the tumor enhanced 28.6% at 2.5 h post intravenous injection of 1. We anticipate that our probe 1 could be employed for T-2-weighted MRI diagnosis of GGT-related cancers in the future when high magnetic field is available in clinic.