Gadolinium-Incorporated Carbon Nanodots for T₁-Weighted Magnetic Resonance Imaging

Abstract

The design and the development of contrast agents for magnetic resonance imaging (MRI), with improved chemical stability and higher contrasting capability for clinical translation, compared to conventional contrast agents, is still of great interest. In this study, a facile and universal approach was explored for controllable functionalization of red-emissive carbon nanodots (RCNDs) with diethylenetriaminepentaacetic anhydride (DTPA) for chelation of gadolinium. A series of accurate characterizations were used to control each step of the synthesis. The functionalization did not alter the band gap of the carbon nanodots, preserving their inherent far-red fluorescence. The as-prepared RCND-DTPA-Gd displayed a high colloidal stability with negligible Gd leakage. The nanodots showed also a better magnetic resonance relaxivity than commercial MRI agents. RCND-DTPA-Gd owned good biocompatibility in vivo even at high doses. Systemically injected RCND-DTPA-Gd were found to be efficiently excreted through the renal route, a feature that further minimizes potential toxicity risks. All these properties suggest that carbon nanodots can be well designed as efficient carriers of Gd, resulting in potential clinical tools as dual MRI/fluorescence functional probes for imaging applications. The approach described here could pave the pathway to a flexible strategy for controllable functionalization of small-size nanoparticles including carbon dots, rendering them more versatile. This work is expected to promote future translation of carbon nanodots into clinical trials.

Bismuth- and gadolinium-codoped carbon quantum dots with red/green dual emission for fluorescence/CT/T1-MRI mode imaging

“…The Bi,Gd-CQD longitudinal relaxivity value ( r 1 ) is 4.29 mM −1 s −1 calculated from the slope of the fitting line, which is significantly larger than that of the commercial T1-weighted contrast agent (Gd-DTPA, r 1 = 3.40 mM −1 s −1 ). 52 This demonstrates that Bi,Gd-CQDs contact water molecules more effectively than Gd-DTPA. Table S2 (ESI†) shows the MRI performance of different Gd-doped nanoparticles compared with other reports.…”

Gadolinium-Doped Carbon Nanodots as Potential Anticancer Tools for Multimodal Image-Guided Photothermal Therapy and Tumor Monitoring

“…A decrease in relaxation times of T 1 was observed as the Gd 3+ concentration increased, consistent with the rise in the relaxation rate R 1 due to the presence of paramagnetic species. This relationship can be described by the formula R 1obs = R 1int + ρ 1 [Gd 3+ ], where R 1obs represents the observed relaxation rate, R 1int is the relaxation rate in the absence of added paramagnetic species, ρ 1 is the longitudinal relaxivity, and [Gd 3+ ] is the Gd concentration. , To determine the relaxivity of ρ 1 , the relaxation rate R 1 was linearly fitted against the Gd 3+ concentration (Figure d). The relaxivity values were found to be 5.0 ± 1.1 mM –1 s –1 at pH 7.4, 6.1 ± 0.7 mM –1 s –1 at pH 6.4, and 11.3 ± 0.2 mM –1 s –1 at pH 5.5.…”

Multifunctional Carbon Nanodots: Enhanced Near‐Infrared Photosensitizing, Photothermal Activity, and Body Clearance

“…CNDs were obtained from a method from our previous reports. [ 13 ] In brief, CNDs were prepared by hydrothermal treatment of PPA. 20 mg of PPA were dispersed in 40 mL of NaOH solution (1 mM).…”

“…[ 11 ] As an example, we previously demonstrated that a targeted intracellular production of ROS could be successfully achieved in tumor cells using folic acid (FA)‐modified photoactive CNDs, [ 12 ] while the covalent functionalization of gadolinium to CND surface allowed multimodal bioimaging. [ 13 ] Chlorin e6 (Ce6) is a second‐generation PS with a high efficacy and low dark toxicity, but its extremely poor water solubility and instability hamper its clinical use. [ 14 ] The combined irradiation of both CNDs and Ce6 could enhance the ROS generation, thus boosting the whole PDT efficiency.…”