Huang Zhongjie, Chen Yicun, Liu Daojun, Lu Chao, Shen Zhiwei, Zhong Shuping, Shi Ganggang
Department of Radiology, The First Affiliated Hospital, Shantou University Medical College Shantou 515041 China
Department of Pharmacology, Shantou University Medical College Shantou 515041 China
RSC Adv. 2018 Jan 30;8(9):5005-5012. doi: 10.1039/c7ra08820e. eCollection 2018 Jan 24.
Core-shell copolymers have received widespread attention because of their unique properties, such as suitable for surface modification and increasing the functionality. Thus, they have been increasingly used in many fields including biomedical, pharmaceutical, electronics and optics. Here, a new core-shell copolymer system was developed to synthesize potential blood pool contrast agent (CA) for magnetic resonance imaging (MRI). The novel CA with high relaxivity was synthesized by conjugating gadolinium (Gd) chelators onto star-block copolymer polyethylenimine-grafted poly(l-lysine) (PEI-PLL) nanoparticles (NPs). The relaxivity of PEI-PLL-DTPA-Gd NPs measured on a 7.0 T small animal MRI scanner was 8.289 mM s, higher than that of contrast agents widely used in the clinic, such as Gd-DTPA (also known as Magnevist, = 4.273 mM s). These results show that PEI-PLL-DTPA-Gd exhibits more efficient MR contrast enhancement compared to Gd-DTPA. More importantly, the PEI-PLL-DTPA-Gd core-shell NPs exhibited extremely low toxicity when measured against the HepG2 cell line over a similar concentration rang of Magnevist. In experiments, PEI-PLL-DTPA-Gd not only displayed good contrast enhancement for the abdominal aorta, but also showed prolonged blood circulation time compared with Gd-DTPA, which should enable longer acquisition time, for MR and MR angiographic images, with high resolution in clinical practice. PEI-PLL-DTPA-Gd NPs have potential to serve as high relaxivity blood pool MRI CA in the clinic.
核壳共聚物因其独特的性能，如适用于表面改性和增加功能性，而受到广泛关注。因此，它们已越来越多地应用于包括生物医学、制药、电子和光学在内的许多领域。在此，开发了一种新的核壳共聚物体系，以合成用于磁共振成像（MRI）的潜在血池造影剂（CA）。通过将钆（Gd）螯合剂缀合到星型嵌段共聚物聚乙烯亚胺接枝聚（L-赖氨酸）（PEI-PLL）纳米颗粒（NPs）上，合成了具有高弛豫率的新型CA。在7.0 T小动物MRI扫描仪上测量的PEI-PLL-DTPA-Gd NPs的弛豫率为8.289 mM s，高于临床广泛使用的造影剂，如Gd-DTPA（也称为马根维显，= 4.273 mM s）。这些结果表明，与Gd-DTPA相比，PEI-PLL-DTPA-Gd表现出更有效的MR造影增强。更重要的是，在与马根维显相似的浓度范围内对HepG2细胞系进行测量时，PEI-PLL-DTPA-Gd核壳NPs表现出极低的毒性。在实验中，PEI-PLL-DTPA-Gd不仅对腹主动脉显示出良好的造影增强，而且与Gd-DTPA相比，还显示出更长的血液循环时间，这在临床实践中应能实现更长的采集时间，用于高分辨率的MR和MR血管造影图像。PEI-PLL-DTPA-Gd NPs有潜力在临床上用作高弛豫率血池MRI CA。
