Wang Yiqing, Tan Xiao, Usman Adil, Zhang Yuhao, Sawczyk Michał, Král Petr, Zhang Cheng, Whittaker Andrew K
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD 4072, Australia.
ACS Macro Lett. 2022 Oct 18;11(10):1195-1201. doi: 10.1021/acsmacrolett.2c00414. Epub 2022 Sep 15.
A major challenge in the preparation of polymeric F magnetic resonance imaging (MRI) contrast agents (CAs) is signal attenuation caused by reduced segmental mobility of partly fluorinated polymers possessing large numbers of fluorine atoms. Previous studies have thus mainly focused on the development of fluorinated segments for improved F MRI; however, detailed investigations of the role of hydrophilic segments on imaging performance remain scarce. In this study, three hydrophilic and biocompatible monomers, i.e., 2-(methylsulfinyl)ethyl acrylate (MSEA), oligo(ethylene glycol) methyl ether acrylate (OEGA), and oligo(2-methyl-2-oxazoline) acrylate (OMOXA), were used to prepare perfluoropolyether (PFPE)-containing amphiphilic block polymers through reversible addition-fragmentation chain-transfer (RAFT) polymerization. The effect of the different hydrophilic segments on F imaging performance was explored. The three polymers could be readily dissolved in aqueous solutions, forming assemblies with the hydrophobic PFPE as the core and the hydrophilic chains as the shell. Molecular dynamics simulations demonstrate that the POMOXA chains adopt a rigid, extended conformation, leading to a relatively short F NMR spin-spin relaxation time (), lower NMR detectable F spins (i.e., visibility), and the least intense F MRI signal. In contrast, although PMSEA-PFPE has a shorter F NMR than POEGA-PFPE, the much higher F spin visibility enhances its MRI signal intensity. The result confirms the importance of maintaining both high fluorine visibility and long relaxation time to prepare effective CAs and highlight the key role of the nonfluorinated hydrophilic segments in determining these parameters.
制备含氟聚合物磁共振成像（MRI）造影剂（CAs）的一个主要挑战是，大量氟原子的部分氟化聚合物链段迁移率降低导致信号衰减。因此，以往的研究主要集中在开发用于改善氟MRI的氟化链段；然而，关于亲水性链段对成像性能作用的详细研究仍然很少。在本研究中，使用三种亲水性和生物相容性单体，即丙烯酸2-（甲基亚磺酰基）乙酯（MSEA）、聚乙二醇甲基醚丙烯酸酯（OEGA）和聚（2-甲基-2-恶唑啉）丙烯酸酯（OMOXA），通过可逆加成-断裂链转移（RAFT）聚合制备了含全氟聚醚（PFPE）的两亲性嵌段聚合物。探讨了不同亲水性链段对氟成像性能的影响。这三种聚合物可以很容易地溶解在水溶液中，形成以疏水性PFPE为核、亲水性链为壳的聚集体。分子动力学模拟表明，POMOXA链呈刚性伸展构象，导致相对较短的氟核磁共振自旋-自旋弛豫时间（）、较低的核磁共振可检测氟自旋（即可见度）和最弱的氟MRI信号。相比之下，尽管PMSEA-PFPE的氟核磁共振弛豫时间比POEGA-PFPE短，但更高的氟自旋可见度增强了其MRI信号强度。该结果证实了保持高氟可见度和长弛豫时间对于制备有效造影剂的重要性，并突出了非氟化亲水性链段在确定这些参数中的关键作用。
