Glutathione-mediated drug release from Tiopronin-conjugated gold nanoparticles for acute liver injury therapy

Tiopronin-conjugated gold nanoparticles (TPN@GNPs), with glutathione (GSH)-responsive drug release property, were developed for acute liver injury therapy. The TPN@GNPs were prepared using a one-pot synthesis method and characterized by UV–vis and transmission electronic microscopy methods. The TPN@GNPs displayed typical surface plasmon resonance of nanogold with a narrow size distribution (ca. 2 nm). The in vitro drug release profiles of the conjugates indicated that TPN@GNPs were able to release TPN in a sustained fashion for 4 h at a simulated intracellular level of GSH. pH values or ionic strengths of the release media had no obvious influence on TPN release from the surface of nanoparticles. The pharmacokinetic studies in rats showed that the TPN@GNPs had longer MRT (7.71 h) than TPN (3.96 h), indicating sustained release pattern of TPN@GNPs in vivo. The sustained release of TPN at the relative high GSH concentration could ameliorate the instability of TPN and enable the drug release in the target cells. Although the IC50 value of TPN@GNPs with TPN/AuCl4− of 3:1 (mol/mol) showed slight increase in comparison with that of the free TPN in HepG2 cells (1.26 ± 1.07 vs. 1.73 ± 1.16 mg/mL), the TPN@GNPs displayed better effects over TPN in the treatment of acute liver injury in vivo. In a liver injury mice model induced by CCl4, the histological analysis showed both the TPN@GNPs and free TPN group could repair the liver injury. In addition, the biochemical parameters showed TPN@GNPs could reduced the aminotransferase to a lower level compared with TPN, which might be due to the sustained drug release and passive liver targeting properties of TPN@GNPs. It demonstrated that gold nanoparticle-based drug delivery system allowed smart functions and superior properties by taking advantages of the unique small size effects and surface chemical properties.

Tiopronin-conjugated gold nanoparticles (TPN@GNPs), with glutathione (GSH)-responsive drug release property, were prepared by one-pot synthesis method for the therapeutic application to the acute liver injury in mice. It showed much better treatment on the acute liver injury compared with conventional TPN injection, which is due to the passive target TPN@GNPs to liver by the EPR effect of gold nanoparticles and GSH-mediated TPN release after the conjugates were uptake by liver cells. It demonstrates that gold nanoparticle-based drug delivery system allows smart functions and superior properties by taking advantages of the unique small size effects and surface chemical properties.Figure optionsDownload high-quality image (136 K)Download as PowerPoint slide