Amphiphilic block polymer-gadolinium conjugates: Design, synthesis and application as efficient and safe nanoscale magnetic resonance imaging contrast agents

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2021-07, Vol.416, p.129170, Article 129170
• Main Authors: Wang, Bing, Li, Haonan, Li, Zhiqian, Luo, Qiang, Gu, Zhongwei, Zhang, Hu, Gong, Qiyong, Luo, Kui
• Format: Article
• Language: English
• Subjects: Magnetic resonance angiography; Morphology; MRI contrast agent; Self-assembly; Tumor imaging
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2021.129170

Linear and cross-linked amphiphilic block polymer-gadolinium conjugates were prepared, and their self-assembled systems with spherical or worm-like morphology were comparatively investigated as efficient and safe MR contrast agents. [Display omitted] •Two-step RAFT polymerization and cross-linking to fabricate amphiphilic polymers.•Modulating the self-assembled morphology by altering the cross-linking degree.•A higher r1 value and better tumor contrast enhancement from the spherical agent.•Sharper MR images of terminal branched vessels in the liver from the worm-like agent. Although polymer-gadolinium conjugates-based contrast agents (CAs) have shown great promise in safe and efficient magnetic resonance imaging (MRI), very few studies on the use of self-assembled polymers to prepare CAs have been reported. The effect of the self-assembled architectural structures of CAs on their MRI performance remains unclear. Herein, two block amphiphilic polymer-gadolinium conjugates (Linear Agent and Cross-Linked Agent3) were designed and fabricated via an approach of two-step reversible addition-fragmentation chain transfer (RAFT) polymerization and cross-linking. These conjugates self-assembled into nanoscale CAs with a spherical or worm-like morphology. These CAs had low toxicity and great hemocompatibility. Both of them displayed an evident increase in the longitudinal relaxivity and the blood circulation time over small molecular CAs (i.e., Gd-DTPA). Linear Agent exhibited superior MRI signal enhancement to Cross-Linked Agent3 in both subcutaneous and orthotopic breast tumor sites. Cross-Linked Agent3 was easily uptaken by tumor cells, but its tumor-specific responsive degradation contributed to a decrease in its MRI efficiency. In the major organs, two agents were able to generate clear and long-lasting images. Moreover, their long residence time in the blood endowed them as magnetic resonance angiography (MRA) agents. A large number of blood vessels, including liver vessels and kidney vessels, could be clearly observed after injection of both CAs, and the contrast-enhanced MR signals in these vessels lasted for over 4 h. Cross-Linked Agent3 excelled over Linear Agent in displaying the terminal of branch blood vessels in the liver and kidney. Overall, the strategy to prepare self-assembled CAs with tunable morphologies would allow a better understanding of the structure–function relationship of these CAs and provide insights into novel designs of polymer-gadolin