Zu Guangyue, Kuang Ye, Dong Jingjin, Cao Yi, Wang Kewei, Liu Min, Luo Liqiang, Pei Renjun
CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
J Mater Chem B. 2017 Jul 7;5(25):5001-5008. doi: 10.1039/c7tb01202k. Epub 2017 Jun 7.
Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. Herein, a multi-arm star-branched polymer was prepared by conjugating oligolysine onto a rigid hyperbranched poly(amido amine) core via click chemistry, followed by covalent modification with Gd chelate and folic acid (FA-OLL-g-HBPAMAM-DTPA-Gd). This multi-arm star-branched polymer contrast agent exhibited much higher longitudinal relaxivity (r = 13.34 mM s) as compared to a commercial contrast agent (Gd-DTPA, r = 4.2 mM s). No obvious histological toxicity was observed from histological assessment, which illustrated that FA-OLL-g-HBPAMAM-DTPA-Gd exhibited excellent biocompatibility. Both in vitro and in vivo MRI studies showed that the macromolecular contrast agent provided better signal contrast enhancement and presented obvious target specificity to KB xenografts with a sufficient time window for MRI scanning; moreover, this multi-arm star-branched mCA has great potential for developing sensitive and biocompatible MRI CA with targeting ability.
具有高效性和安全性的造影剂是磁共振成像探针的理想选择。在此，通过点击化学将寡聚赖氨酸连接到刚性超支化聚（酰胺胺）核上，随后用钆螯合物和叶酸进行共价修饰，制备了一种多臂星形支化聚合物（FA-OLL-g-HBPAMAM-DTPA-Gd）。与商业造影剂（钆-DTPA，r = 4.2 mM s）相比，这种多臂星形支化聚合物造影剂表现出更高的纵向弛豫率（r = 13.34 mM s）。组织学评估未观察到明显的组织毒性，这表明FA-OLL-g-HBPAMAM-DTPA-Gd具有优异的生物相容性。体外和体内磁共振成像研究均表明，大分子造影剂提供了更好的信号对比增强，对KB异种移植瘤具有明显的靶向特异性，且有足够的时间窗口进行磁共振成像扫描；此外，这种多臂星形支化大分子造影剂在开发具有靶向能力的灵敏且生物相容的磁共振成像造影剂方面具有巨大潜力。
