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 T₁-dominated CAs in clinic but using intracellularly formed Gd nanoparticles to enhance the T₂-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 γ-glutamyltranspeptidase (GGT) cleavage and an intracellular CBT-Cys condensation reaction to form Gd nanoparticles (i.e., 1-NPs) to enhance the T₂-weighted MR contrast of tumor in vivo at 9.4 T. Living cell experiments indicated that the 1-treated HeLa cells had an r₂ value of 27.8 mM^–1 s^–1 and an r₂/r₁ ratio of 10.6. MR imaging of HeLa tumor-bearing mice indicated that the T₂ 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 T₂-weighted MRI diagnosis of GGT-related cancers in the future when high magnetic field is available in clinic.

中文翻译：

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γ-谷氨酰转肽酶触发的细胞内Ga纳米颗粒形成增强了肿瘤的T ₂加权MR对比度

磁共振成像（MRI）在诊断深部内部癌症方面具有优势，但是始终需要造影剂（CAs）来提高MRI敏感性。基于clinic （Gd）的药物在临床上通常用作T ₁为主的CA，但尚未报道使用细胞内形成的Gd纳米颗粒在高磁场下增强体内肿瘤的T ₂加权MRI 。在这里，我们合理地设计了一个“智能”的基于Gd的探针Glu-Cys（StBu）-Lys（DOTA-Gd）-CBT（1），将其进行了γ-谷氨酰转肽酶（GGT）裂解和细胞内CBT-Cys缩合反应形成Gd纳米颗粒（即1-NPs）以增强肿瘤的T ₂加权MR对比在9.4 T体内进行活细胞实验。活细胞实验表明，经1处理的HeLa细胞的r ₂值为27.8 mM ^–1 s ^–1，r ₂ / r _1的比率为10.6。HeLa荷瘤小鼠的MR成像表明，在静脉注射1的2.5 h后，肿瘤的T ₂ MR对比增强了28.6％。我们预计，当临床中可以使用强磁场时，将来我们的探针1可以用于T ₂加权MRI诊断GGT相关癌症。