γ-Glutamyltranspeptidase-Triggered Intracellular Gadolinium Nanoparticle Formation Enhances the T2-Weighted MR Contrast of Tumor.
Zijuan HaiYanhan NiDilizhatai SaimiHongyi YangHaiyang TongKai ZhongGaolin LiangPublished in: Nano letters (2019)
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.
Keyphrases
- contrast enhanced
- magnetic resonance imaging
- magnetic resonance
- computed tomography
- diffusion weighted imaging
- primary care
- crispr cas
- young adults
- cell proliferation
- pet imaging
- adipose tissue
- mesenchymal stem cells
- oxidative stress
- high dose
- low dose
- quantum dots
- bone marrow
- insulin resistance
- metabolic syndrome
- drug induced
- network analysis
- dna binding
- transcription factor