Glutathione-Responsive Gold Nanoparticles as Computed Tomography Contrast Agents for Hepatic Diseases

Abstract

Glutathione (GSH) is produced at high levels in the normal liver, but its production is considerably reduced under certain pathological conditions. Accordingly, an imaging probe capable of visualizing the altered GSH level in the liver would be a useful tool for monitoring hepatic functions or diseases. Here, we report a gold nanoparticle (AuNP)-based computed tomography (CT) contrast agent that undergoes a change in colloidal stability in response to GSH levels, resulting in differential CT signal intensity between normal (higher intensity) and pathological (lower intensity) livers, enabling imaging of hepatic function. This GSH-responsive CT contrast agent, prepared by coating AuNPs with PEGylated bilirubin (PEG-BR), shows serum stability and high sensitivity to GSH. The resulting poly(ethylene glycol) (PEG)-BR@AuNPs preferentially accumulate in the normal liver, as evidenced by strongly enhanced CT intensity, but fail to do so in a GSH-depleted mouse model, where the CT signal in the liver was substantially decreased. In addition, injection of PEG-BR@AuNPs caused a greater reduction in CT signals in the liver in a drug-induced acute liver failure model than in healthy normal mice. These findings suggest that GSH-responsive PEG-BR@AuNPs have the potential to be used as a CT contrast agent to detect various hepatic function-related diseases and liver-metastasized tumors.