4.8 Article

Redox-Activated Contrast-Enhanced T1-Weighted Imaging Visualizes Glutathione-Mediated Biotransformation Dynamics in the Liver

Journal

ACS NANO
Volume 15, Issue 11, Pages 17831-17841

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c06026

Keywords

redox-activated probes; glutathione; biotransformations; magnetic resonance imaging; liver functions

Funding

  1. National Natural Science Foundation of China [22125702, 92059109, 22077107, 21771148, 21521004]
  2. Natural Science Foundation of Fujian Province of China [2020J02001]
  3. Youth Innovation Funding Program of Xiamen City [3502Z20206051]
  4. Fundamental Research Funds for the Central Universities [20720200005]

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The study introduces a novel type of nanomaterial as redox-activated probes for real-time visualization of GSH-mediated liver biotransformation using MRI. The technique reveals periodic variations in GSH concentration during the degradation of the nanoparticles, providing direct imaging evidence for carrier-mediated processes in GSH metabolism. This methodology offers a feasible means for in-depth investigations of GSH-related biological processes in liver and real-time assessment of liver functions for early diagnosis of diseases and toxicity evaluation of pharmaceuticals.
GSH-mediated liver biotransformation is a crucial physiological process demanding efficient research tools. Here, we report a type of amorphous FexMnyO nanoparticles (AFMO-ZDS NPs) as redox-activated probes for in vivo visualization of the dynamics of GSH-mediated biotransformation in liver with T-1-weighted magnetic resonance imaging (MRI). This imaging technique reveals the periodic variations in GSH concentration during the degradation of AFMO-ZDS NPs due to the limited transportation capacity of GSH carriers in the course of GSH efflux from hepatocytes to perisinusoidal space, providing direct imaging evidence for this important carrier-mediated process during GSH-mediated biotransformation. Therefore, this technique offers an effective method for in-depth investigations of GSH-related biological processes in liver under various conditions as well as a feasible means for the real-time assessment of liver functions, which is highly desirable for early diagnosis of liver diseases and prompt a toxicity evaluation of pharmaceuticals.

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