Sensitive T2 MRI Contrast Agents from the Rational Design of Iron Oxide Nanoparticle Surface Coatings
Sensitive T2 MRI Contrast Agents from the Rational Design of Iron Oxide Nanoparticle Surface Coatings
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DOI：
10.1021/acs.jpcc.2c05390
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发表时间：
2023-01-19
影响因子：
3.7
通讯作者：
Colvin, Vicki L.
中科院分区：
文献类型：
--
作者：
Cho, Minjung;Villanova, Jake;Colvin, Vicki L.
氧化铁纳米粒子是 FDA 批准的、不含钆的传统磁共振成像 (MRI) 造影剂的替代品。虽然它们的磁芯负责 T2 对比度，但颗粒界面处的非磁性聚合物会影响颗粒附近大量水的扩散。我们在这里展示了这种相互作用如何改变水质子的弛豫动力学，从而改变纳米粒子的对比度性能。不同核心直径和表面涂层的氧化铁纳米晶体库可以形成生物相容性、非细胞毒性和胶体稳定的悬浮液，具有优异的 MRI 性能。聚合物涂层的接枝密度和厚度都会影响水质子在纳米颗粒周围停留的时间，从而影响它们的造影剂性能。这些材料的直径相关对比度性能的表征表明，具有致密亲水性聚合物涂层的纳米颗粒在比其他系统更小的尺寸下达到了静态移相状态和最佳 T2 弛豫率。我们认为，这种涂层为磁性颗粒附近的水扩散提供了一个缓慢的隔间，从而导致有效扩散常数低于散装水。通过同时控制表面涂层和核心直径，我们可以生成一种具有有史以来报道的最大 T2 弛豫率之一（510 mM-1 s-1）的孤立纳米晶体材料。这个概念框架可以解释此类T2造影剂以及现有文献中已经报道的复杂的结构-性能趋势。氧化铁纳米晶体 (IONC) 界面的水扩散是设计敏感且可能响应的 T2 MRI 造影剂的重要考虑因素。
Iron oxide nanoparticles are an FDA-approved and gadolinium-free alternative to conventional magnetic resonance imaging (MRI) contrast agents. While their magnetic cores are responsible for T2 contrast, the nonmagnetic polymers at the particle interfaces can affect the diffusion of bulk water near the particles. We show here how this interaction can alter the relaxation dynamics of water protons and, consequently, the nanoparticle's contrast performance. Libraries of iron oxide nanocrystals of different core diameters and surface coatings can form biocompatible, non-cytotoxic, and colloidally stable suspen-sions with excellent MRI properties. Both the grafting density and thickness of polymer coatings influence the amount of time water protons spend around a nanoparticle and thus their contrast agent performance. Characterization of the diameter-dependent contrast performance of these materials revealed that nanoparticles with dense, hydrophilic polymer coatings reached the static dephasing regime, and optimal T2 relaxivity, at smaller dimensions than other systems. We rationalized that such coatings offered a slow compartment for water diffusion near the magnetic particle, resulting in an effective diffusion constant lower than bulk water. By manipulating the surface coating and core diameter together, we could generate a material with one of the largest T2 relaxivities ever reported (510 mM-1 s-1) for an isolated nanocrystal. This conceptual framework can explain the complex structure-performance trends of this class of T2 contrast agents and those already reported in the existing literature. Water diffusion at iron oxide nanocrystals (IONCs) interfaces is an essential consideration in designing sensitive and possibly responsive T2 MRI contrast agents.