Si Ge, Hapuarachchige Sudath, Artemov Dmitri
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States; The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, United States.
The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, United States; Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21287, United States.
ACS Appl Nano Mater. 2022 Jul 22;5(7):9625-9632. doi: 10.1021/acsanm.2c01835. Epub 2022 Jun 30.
Ultrasmall superparamagnetic iron oxide nanoparticles (uSPIOs) are attractive platforms for the development of smart contrast agents for magnetic resonance imaging (MRI). Oleic acid-capped uSPIOs are commercially available yet hydrophobic, hindering applications. A hydrophilic ligand with high affinity toward uSPIO surfaces can render uSPIOs water-soluble, biocompatible, and highly stable under physiological conditions. A small overall hydrodynamic diameter ensures optimal pharmacokinetics, tumor delivery profiles, and, of particular interest, enhanced MR contrasts. In this study, for the first time, we synthesized a ligand that not only fulfills the as-proposed properties but also provides multiple reactive groups for further modifications. The synthesis delivers a facile approach using commercially available reactants, with resultant uSPIO-ligand constructs assembled through a single-step ligand exchange process. Structural and molecular size analyses confirmed size uniformity and small hydrodynamic diameter of the constructs. On average, 43 reactive amine groups were present per uSPIO nanoparticle. Its relaxivity has been tested on a 7 Tesla MR instrument and is comparable to that of the clinically available gadolinium-based contrast agent GBCA (1 vs 3 mM s, respectively). A significant decrease in tumor 1 (15%) within 1 h of injection and complete signal recovery after 2 h were detected with a dose of 7 g Fe/g mouse. The agent also has high relaxivity and can be used for contrast-enhanced MRI. Taken together, good relaxation and delivery properties and the presence of multiple surface reactive groups can facilitate its application as a universal MRI-compatible nanocarrier platform.
超小超顺磁性氧化铁纳米颗粒（uSPIOs）是用于开发磁共振成像（MRI）智能造影剂的有吸引力的平台。油酸包覆的uSPIOs有商业产品，但具有疏水性，这阻碍了其应用。一种对uSPIO表面具有高亲和力的亲水性配体可使uSPIOs具有水溶性、生物相容性，并在生理条件下高度稳定。较小的整体流体动力学直径可确保最佳的药代动力学、肿瘤递送情况，特别值得关注的是，可增强磁共振对比度。在本研究中，我们首次合成了一种配体，它不仅满足上述特性，还提供多个反应基团用于进一步修饰。该合成方法使用市售反应物，操作简便，通过一步配体交换过程组装得到uSPIO-配体构建体。结构和分子大小分析证实了构建体的大小均匀性和较小的流体动力学直径。每个uSPIO纳米颗粒平均存在43个反应性胺基。其弛豫率已在7特斯拉磁共振仪器上进行测试，与临床可用的钆基造影剂GBCA相当（分别为1和3 mM s）。以7 g Fe/g小鼠的剂量注射后，在1小时内肿瘤信号显著降低（15%），2小时后信号完全恢复。该造影剂还具有高弛豫率，可用于增强磁共振成像。综上所述，良好的弛豫和递送特性以及多个表面反应基团的存在可促进其作为通用的MRI兼容纳米载体平台的应用。
