Magnetic resonance energy transfer for in vivo glutathione susceptibility weighted imaging

Glutathione (GSH) plays a vital role in maintaining biological redox homeostasis. Accordingly, accurate imaging of glutathione in vivo is of great significance. Herein, we propose a magnetic resonance energy transfer (MRET) strategy based on a distance-dependent magnetic exchange coupling effect (MECE), which can realize GSH detection within tumors in vivo by susceptibility weighted imaging (SWI). Fe₃O₄ nanoparticles (NPs) and CoFe₂O₄ NPs linked with cystamine (Fe₃O₄–S–S–CoFe₂O₄) have been successfully designed as SWI nanoprobes. After the disulfide bonds are broken by excess GSH in the tumor, the increase in the distance between Fe₃O₄ NPs and CoFe₂O₄ NPs will induce a decrease of MECE and magnetic susceptibility. As a result, the changes in the SWI signals are used for tumor GSH detection in vivo. Experimental results in vitro and in vivo demonstrate that the Fe₃O₄–S–S–CoFe₂O₄ SWI nanoprobe can sensitively detect concentrations of GSH in tumors. Hence, this strategy not only improves the sensitivity of the GSH response in SWI but also provides a powerful basis for the design of other responsive functional MRI nanoprobes.