优化 RAFT 聚合共聚物中的钆-DOTA 负载,为老化血脑屏障提供优质磁共振成像

IF 3.5 Q2 CHEMISTRY, ANALYTICAL
Hunter A. Miller, Aaron Priester, Evan T. Curtis, Krista Hilmas, Ashleigh Abbott, Forrest M. Kievit and Anthony J. Convertine
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引用次数: 0

摘要

钆基造影剂(GBCAs)的开发在推动磁共振成像(MRI)方面发挥了关键作用,它能在不暴露于电离辐射的情况下增强软组织造影效果。尽管钆基造影剂已广泛应用于临床,但对改进型钆基造影剂的需求促使配体化学和聚合物科学不断创新。我们报告了一种使用甲基丙烯酸酯功能化 DOTA 配体,通过直接可逆加成-碎片链转移(RAFT)聚合合成一系列共聚物的新方法。这种技术可以精确控制聚合物中的钆含量,省去了后续的共轭和纯化步骤,并有利于添加靶向配体等其他成分。对所得共聚物的弛豫特性进行了分析,结果表明,钆-DOTA 的具体装载量在 12-30 摩尔% 之间,能产生最佳的磁共振成像对比度增强效果。电感耦合等离子体 (ICP) 测量证实了这些发现,揭示了钆含量与弛豫性之间的非线性关系。优化后的共聚物与 claudin-1 靶向肽 C1C2 合成,在老龄小鼠的 BBB 靶向成像中显示出成像效用。这项研究为开发更高效的 GBCA 添加到共聚物中,用于靶向给药和生物成像应用提供了一条前景广阔的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Optimized gadolinium-DO3A loading in RAFT-polymerized copolymers for superior MR imaging of aging blood–brain barrier†

Optimized gadolinium-DO3A loading in RAFT-polymerized copolymers for superior MR imaging of aging blood–brain barrier†

The development of gadolinium-based contrast agents (GBCAs) has been pivotal in advancing magnetic resonance imaging (MRI), offering enhanced soft tissue contrast without ionizing radiation exposure. Despite their widespread clinical use, the need for improved GBCAs has led to innovations in ligand chemistry and polymer science. We report a novel approach using methacrylate-functionalized DO3A ligands to synthesize a series of copolymers through direct reversible addition-fragmentation chain transfer (RAFT) polymerization. This technique enables precise control over the gadolinium content within the polymers, circumventing the need for subsequent conjugation and purification steps, and facilitates the addition of other components such as targeting ligands. The resulting copolymers were analysed for their relaxivity properties, indicating that specific gadolinium-DO3A loading contents between 12–30 mole percent yield optimal MRI contrast enhancement. Inductively coupled plasma (ICP) measurements corroborated these findings, revealing a non-linear relationship between gadolinium content and relaxivity. Optimized copolymers were synthesized with the claudin-1 targeting peptide, C1C2, to image BBB targeting in aged mice to show imaging utility. This study presents a promising pathway for the development of more efficient GBCA addition to copolymers for targeted drug delivery and bioimaging application.

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CiteScore
2.30
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