School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Langmuir. 2023 Feb 14;39(6):2171-2181. doi: 10.1021/acs.langmuir.2c02621. Epub 2023 Feb 3.
Superparamagnetic iron oxide nanoparticles, MNPs, are under investigation as stimulus-responsive nanocarriers that can be tracked by magnetic resonance imaging. However, fundamental questions remain, including the effect of differing surface chemistries on MR image contrast efficacy (relaxivity), both initially and over time in the biological environment. The effects of pH and ligand type on the relaxivity of electrostatically and sterically stabilized spherical 8.8 nm superparamagnetic MNP suspensions are described. It is shown for the first time that across the pH ranges, within which the particles are fully dispersed, increasing acidity progressively reduces relaxivity for all ligand types. This effect is stronger for electrostatically (citrate or APTES) than for sterically stabilized (PEG5000) MNPs. NMR relaxation profiles (relaxivity as a function of H Larmor frequency) identified an inner-sphere effect, arising from the protonation of bare oxide or low-molecular-weight-bound species, as the cause. The suppression is not accounted for by the accepted model (SPM theory) and is contrary to previous reports of increased relaxivity at lower pH for paramagnetic iron oxide nanoparticles. We propose that the suppression arises from the orientation of water molecules, with the oxygen atom facing the surface increasingly preferred with increasing surface protonation. For APTES-stabilized MNPs, pendant amines and the silane layer confer exceptional chemical and colloidal stability at low pH. Dissolution of these particles at pH 1.8 was monitored over several months by combining in situ measurements of relaxation profiles with dynamic light scattering. It was shown that particles are magnetically intact for extended periods until they rapidly dissolve, once the silane layer is breached, in a process that is apparently second order in particle concentration. The findings are of interest for tracking MNP fate, for quantitation, and for retention of magnetic responsiveness in biological settings.
超顺磁氧化铁纳米颗粒（MNPs）作为刺激响应性纳米载体正在研究中，这些载体可以通过磁共振成像来追踪。然而，仍存在一些基本问题，包括不同表面化学性质对磁共振成像对比效能（弛豫率）的影响，包括在生物环境中初始和随时间的影响。本文描述了 pH 值和配体类型对静电和空间稳定的 8.8nm 超顺磁 MNPs 悬浮液弛豫率的影响。首次表明，在颗粒完全分散的 pH 范围内，随着酸度的增加，所有配体类型的弛豫率都逐渐降低。对于静电（柠檬酸盐或 APTES）稳定的 MNPs 比空间稳定（PEG5000）的 MNPs 影响更强。NMR 弛豫曲线（弛豫率作为 H Larmor 频率的函数）确定了内球效应，这是由裸露氧化物或低分子量结合物的质子化引起的。这种抑制作用不能用公认的模型（SPM 理论）来解释，也与先前报道的低 pH 值下顺磁性氧化铁纳米颗粒的弛豫率增加的情况相反。我们提出，这种抑制作用是由于水分子的取向引起的，随着表面质子化程度的增加，氧原子面向表面的方向越来越受到青睐。对于 APTES 稳定的 MNPs，悬垂胺和硅烷层在低 pH 值下赋予了其特殊的化学和胶体稳定性。通过将弛豫曲线的原位测量与动态光散射相结合，监测了在 pH 1.8 下几个月内这些颗粒的溶解情况。结果表明，在硅烷层被破坏之前，颗粒在很长一段时间内保持磁性完整，一旦硅烷层被破坏，溶解过程显然是颗粒浓度的二级反应。这些发现对于跟踪 MNPs 的命运、定量以及在生物环境中保持磁性响应能力都很有意义。
