Synergistic Effect of Oxygen- and Nitrogen-Containing Groups in Graphene Quantum Dots: Red Emitted Dual-Mode Magnetic Resonance Imaging Contrast Agents with High Relaxivity.

Abstract

Contrast agents (CAs) in magnetic resonance imaging generally involve the dissociative Gd3+. Because of the limited ligancy of Gd3+, the balance between Gd3+ coordination stability (reducing the concentration of dissociative Gd3+) and increases in the number of coordination water molecules (enhancing the relaxivity) becomes crucial. Herein, the key factor of the synergistic effect between the O- and N-containing groups of graphene quantum dots for the structural design of CAs with both high relaxivity and low toxicity was obtained. The nitrogen-doped graphene quantum dots (NGQDs) with an O/N ratio of 0.4 were selected to construct high-relaxivity magnetic resonance imaging (MRI)-fluorescence dual-mode CAs. The coordination stability of Gd3+ can be increased through the synergetic coordination of O- and N-containing groups. The synergetic coordination of O- and N-containing groups can result in the short residency time of the water ligand and achieve high relaxivity. The resulting CAs (called NGQDs-Gd) exhibit a high relaxivity of 32.04 mM-1 s-1 at 114 μT. Meanwhile, the NGQDs-Gd also emit red fluorescence (614 nm), which can enable the MRI-fluorescence dual-mode imaging as the CAs. Moreover, the bio-toxicity and tumor-targeting behavior of NGQDs-Gd were also evaluated, and NGQDs-Gd show potential in MRI-fluorescence imaging in vivo.