A tumor-targeting and ROS-responsive iron-based T 1 magnetic resonance imaging contrast agent for highly specific tumor imaging.

T 1 contrast agents (CAs) exhibit outstanding capacity in enhancing the magnetic resonance imaging (MRI) contrast between tumor tissues and normal tissues for generating bright images. However, the clinical application of representative gadolinium(III) chelate-based T 1 CAs is limited due to their potential toxicity and low specificity for pathological tissues. To obtain MRI CAs with a combination of low toxicity and high tumor specificity, herein, we report a reactive oxygen species (ROS)-responsive T 1 CA (GA-Fe(II)-PEG-FA), which was constructed by chelating Fe(II) with gallic acid (GA), and modified with tumor-targeted folic acid (FA). The resultant CA could accumulate in tumor tissues via the affinity between FA and their receptors on the tumor cell membrane. It realized the switch from Fe(II) to Fe(III), and further enhancing the longitudinal relaxation rate ( r 1 ) under the stimuli of ROS in the tumor microenvironment. The r 1 of GA-Fe(II)-PEG-FA on a 0.5 T nuclear magnetic resonance analyzer increased to 2.20 mM -1 s -1 under ROS stimuli and was 5 times greater than the r 1 (0.42 mM -1 s -1 ) before oxidation. The cell and in vivo experiments demonstrated that GA-Fe(II)-PEG-FA exhibited good biocompatibility and significant targeting specificity to tumor cells and tumor tissues. Furthermore, in vivo MRI studies demonstrated that the enhanced T 1 contrast effect against tumors could be achieved after injecting the CA for 3 h, indicating that GA-Fe(II)-PEG-FA has the potential as an ideal tumor MRI CA to increase the contrast and improve the diagnostic precision.