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Nano Lett. 2019 Apr 10;19(4):2428-2433. doi: 10.1021/acs.nanolett.8b05154. Epub 2019 Mar 25.

γ-Glutamyltranspeptidase-Triggered Intracellular Gadolinium Nanoparticle Formation Enhances the T2-Weighted MR Contrast of Tumor.

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Hefei National Laboratory of Physical Sciences at Microscale, Department of Chemistry , University of Science and Technology of China , 96 Jinzhai Road , Hefei , Anhui 230026 , China.
Institutes of Physical Science and Information Technology , Anhui University , 110 Jiulong Road , Hefei , Anhui 230601 , China.
High Magnetic Field Laboratory , Hefei Institutes of Physical Science, Chinese Academy of Sciences , 350 Shushanhu Road , Hefei , Anhui 230031 , China.


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.


T2-weighted magnetic resonance imaging; gadolinium nanoparticle; γ-Glutamyltranspeptidase

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