Liu Guangkuo, Li Xinxin, Liu Xiaojie, Lu Wangting, Xue Yanan, Liu Min
Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology Wuhan 430205 China.
School of Optoelectronic Materials & Technology, Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China.
RSC Adv. 2024 Apr 2;14(15):10499-10506. doi: 10.1039/d4ra00316k. eCollection 2024 Mar 26.
Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist ( = 4.25 mM s) used in clinic, the PC/Ad-PEG-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity ( = 11.62 mM s) with excellent biocompatibility. Furthermore, experiments demonstrated that PC/Ad-PEG-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility . Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.
与小分子造影剂相比，大分子造影剂通常具有出色的造影能力和肿瘤靶向能力，尤其适用于早期肿瘤检测。在此，合成了环糊精共轭的低分子量聚乙烯亚胺作为大分子主链。随后，合成了具有金刚烷末端和钆螯合物的线性聚合物，然后通过主客体相互作用与主链共轭。最后，通过生物正交化学将叶酸共轭到所制备的造影剂上，这赋予了造影剂在肿瘤区域积累的能力。与临床使用的马根维显（弛豫率 = 4.25 mM⁻¹s⁻¹）相比，PC/Ad-PEG-PLL(DTPA-Gd)-FA表现出更高的纵向弛豫率（弛豫率 = 11.62 mM⁻¹s⁻¹），且具有出色的生物相容性。此外，实验表明PC/Ad-PEG-PLL(DTPA-Gd)-FA能够有效地在肿瘤区域积累，并产生比马根维显更亮的图像。苏木精-伊红染色和代谢数据进一步表明这种造影剂具有出色的生物相容性。最后，上述结果表明这种大分子造影剂可能是一种有潜力的用于肿瘤靶向诊断的磁共振成像造影剂候选物。
