State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics , Chinese Academy of Sciences , Wuhan , 430071 , P.R. China.
Department of Chemistry and Biochemistry , National Chung-Cheng University , 168 University Road , Min-Hsiung, Chiayi 621 , Taiwan.
Nano Lett. 2019 Jan 9;19(1):441-448. doi: 10.1021/acs.nanolett.8b04252. Epub 2018 Dec 24.
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 H 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 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.
纳米对比剂（Nano CA）是用于增加医学磁共振成像（MRI）对比度的纳米材料。然而，Nano CA 的相关弛豫机制尚不清楚，并且在弛豫率增强方面几乎没有取得重大突破。本文合成了一种新的亲水性 Gd-DOTA 配合物，并将其与不同链长的 PEG 结合，得到了具有超顺磁性的石墨烯量子点（PGQD）。我们在水溶液中进行了变温变场强 NMR 研究，研究了三种不同链长的 PGQD 的水交换和旋转动力学。具有超顺磁链长的最佳 GQD 在 H NMR 弛豫测量研究中表现出了很好的性能提升。体外实验结果表明，通过调节 PEG 长度可以控制设计的 PGQD 的弛豫率，其弛豫率比目前的商业 MRI 对比剂（如 Gd-DTPA）高约 16 倍，基于“每 Gd”的基准。可以合理地调整纳米对比剂的弛豫率，从而在磁共振成像中获得无与伦比的潜力，例如通过制备具有增强 T1 弛豫率的超顺磁 GQD 来实现。具有合适 PEG 长度的制备 PGQD 在 1.5 T 下具有最佳弛豫率。静脉注射后，其通过实体瘤的摄取过程甚至可以通过临床使用的 1.5 T MRI 扫描仪进行监测。这项研究还将为设计和合成高效的磁共振对比剂提供一个极好的平台。
