Fluorine and Nitrogen Co-Doped Carbon Dot Complexation with Fe(III) as a T Contrast Agent for Magnetic Resonance Imaging.

Commercial gadolinium-based materials have been widely used as contrast agents for magnetic resonance imaging (MRI), but the high toxicity of leaking free Gd ions still raises biosafety concerns. Here, we develop a novel, safe, and efficient MRI contrast agent based on a stable Fe(III) complex of fluorine and nitrogen co-doped carbon dots (F,N-CDs) that was prepared from glucose and levofloxacin by a simple microwave-assisted thermal decomposition method. The obtained Fe@F,N-CD complex exhibits higher longitudinal relaxivity ( r = 5.79 mM·s) than that of the control samples of the Fe@CD complex ( r = 4.23 mM s) and free Fe ( r = 1.59 mM s) in aqueous solution, as assessed by a 1.5 T NMR analyzer. More importantly, the Fe@F,N-CD complex is very stable with a large coordination constant of 1.06 × 10 in aqueous medium. While incubated with HeLa cells, the Fe@F,N-CD complex shows clear MR images, demonstrating that it has potential to be an excellent MRI contrast agent. Furthermore, in vivo MRI experiments indicate that the Fe@F,N-CD complex provides high-resolution MRI pictures of 4T1 tumor bearing BALB/c mice 15 min after injection and can be completely excreted 2 h after administration. No cytotoxicity was observed with F,N-CDs and Fe concentration up to 0.2 mg/mL and 0.3 mM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, respectively. The possible mechanism of the enhanced MRI effect of the Fe@F,N-CD complex is therefore proposed. The extremely low toxicity, high r relaxivity, strong photoluminescence, and low synthetic cost enable the Fe@F,N-CD complex to be a safe and promising T-weighted MRI contrast agent for clinical applications.