Engineered Paramagnetic Graphene Quantum Dots with Enhanced Relaxivity for Tumor Imaging

Abstract

Nano contrast agents (Nano CA) are nanomaterials used to increase contrast in the medical magnetic resonance imaging (MRI). However, the related relaxation mechanism of the Nano CA is not clear yet and little significant breakthrough in relaxivity enhancement has been achieved. Herein, a new hydrophilic Gd-DOTA complex functionalized with different chain length of PEG was synthesized and incorporated into graphene quantum dots (GQD) to obtain paramagnetic graphene quantum dots (PGQD). We performed a variable-temperature and variable-field intensity NMR study in aqueous solution on the water exchange and rotational dynamics of three different chain lengths of PGQD. The optimal GQD with paramagnetic chain length shows a great improvement in performance on 1H NMR relaxometric studies. In vitro results demonstrated that the relaxivity of the designed PGQD could be controlled by regulating the PEG length, and its relaxivity was ∼16 times higher than that of current commercial MRI contrast agents (e.g., Gd-DTPA), on a “per Gd” basis. The relaxivity of the Nano CA can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the paramagnetic GQD with the enhanced T 1 relaxivity. The fabricated PGQDs with suitable PEG length got the best relaxivity at 1.5 T. After intravenous injection, its feeding process by solid tumor could even be monitored by clinically used 1.5 T MRI scanners. This research will also provide an excellent platform for the design and synthesis of highly effective MR contrast agents.

Recent Advances on Graphene Quantum Dots for Bioimaging Applications

“…Among different carriers, GQD is an attractive nanocarrier owing to its biocompatibility, water solubility, and non-toxicity. Recently, Yang et al developed paramagnetic GQDs (PGQDs) by incorporating polyethylene glycol (PEG) functionalized Gd-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA) complex (Yang et al, 2019). Different PEG chains were used for functionalization, and the highest longitudinal relaxivity was achieved from GQD-PEG 12 -Gd, which was about 16-fold higher than the commercial MRI contrast agent (Gd-DTPA).…”

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

“…Thirdly, GDs could be combined with magnetic particles and then introduced into bone repair materials, which could not only make use of the excellent properties of GDs to accelerate bone regeneration, but also enabled that magnetic particles were evenly dispersed and tracked by nuclear magnetic equipment. 53,[160][161][162] For example, Chen et al 53 prepared a composite scaffold containing gelatin/PCL/ultra-small paramagnetic iron oxide/GO (Gel/PCL/USPIO/GO) by freeze-drying. The negatively charged GO could effectively combine with the positively charged USPIO, to ensure that the USPIO provided a stable imaging effect for the scaffolds.…”

Magnetic Nanomaterials as Contrast Agents for MRI

“…In general, the development of these NPs can be divided in two main classes: nanostructured materials (i.e., Gd 2 O 3 , Mn 3 O 4 , Dy 2 O 3 , MnO) with incorporated paramagnetic ions [ 19 , 20 , 21 , 22 , 23 ]; or the postfunctionalization of the NPs with lanthanide coordination complexes. The latter approach has been developed using different nanoparticle scaffolds as supports (quantum dots, gold, silica and micelles), which allow a subsequent doping to be performed with pentetic acid (DTPA), dodecane tetraacetic acid (DOTA), or derivates [ 24 , 25 , 26 , 27 ].…”