Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium.
Contrast Media Mol Imaging. 2011 Jul-Aug;6(4):236-50. doi: 10.1002/cmmi.423. Epub 2010 Dec 29.
Superparamagnetic iron oxide nanoparticles (SPION) are very promising contrast media, especially for molecular imaging, due to their superior NMR efficacy. They even have wider biomedical applications such as in drug and gene delivery, tissue engineering and bioseparation, or as sensitive biological nanosensors. By coupling them to affinity ligands, SPION can bind to drugs, proteins, enzymes, antibodies or nucleotides. For in vitro biomedical applications, the detection of molecular interaction is possible by using a diversity of systems capable of sensing the magnetic properties of these materials. The goal of the present work was to develop and validate various in vitro biomedical applications of ultrasmall superparamagnetic particles of iron oxide (USPIO), including some that are not related to their magnetic properties. USPIO coated with dextran, starch or bisphosphonate exposing carboxylate groups were synthesized and some of them were functionalized by conjugating various biomolecules, such as biotin, streptavidin and apoptosis, or VCAM-1 specific peptides. The in vitro biomedical applications assessed in the present work included: (1) the relaxometric measurement of antibody concentration, cell receptor expression, molecular interaction, and enzymatic activity in aqueous suspensions; (2) MRI visualization of cells and detection of molecular interaction in an ELISA system; (3) ELISA applications of USPIO derivatives; and (4) detection of specific biomolecules by histochemistry. Our results confirm that rapid and simple in vitro detection of a diversity of functionalized SPION with relevance in medicine is possible by the existing NMR techniques and by chemical staining reactions. The protocols can be applied to minimally prepared biological samples (e.g. whole blood, blood plasma or serum, cell suspensions, biopsies, histological preparations, etc.), and often do not need complicated systems of signal amplification. The use of SPION labeled compounds could furthermore contribute to cost reductions in the diagnosis and in patient care.
超顺磁性氧化铁纳米粒子（SPION）是非常有前途的对比剂，特别是在磁共振成像领域，因为它们具有优越的 NMR 效果。它们甚至在更广泛的生物医学领域有应用，如药物和基因传递、组织工程和生物分离，或作为敏感的生物纳米传感器。通过将它们与亲和配体偶联，SPION 可以与药物、蛋白质、酶、抗体或核苷酸结合。对于体外生物医学应用，可以使用各种能够感知这些材料磁性能的系统来检测分子相互作用。本工作的目的是开发和验证超顺磁性氧化铁纳米粒子（USPIO）的各种体外生物医学应用，包括一些与它们的磁性能无关的应用。用葡聚糖、淀粉或双膦酸盐合成了带负电荷的羧基暴露的 USPIO，并对其中一些进行了功能化，使其与各种生物分子（如生物素、链霉亲和素和凋亡或 VCAM-1 特异性肽）偶联。本工作评估的体外生物医学应用包括：（1）在水悬浮液中测量抗体浓度、细胞受体表达、分子相互作用和酶活性的弛豫测量；（2）在 ELISA 系统中可视化细胞和检测分子相互作用的 MRI；（3）USPIO 衍生物的 ELISA 应用；（4）通过组织化学检测特定生物分子。我们的结果证实，通过现有的 NMR 技术和化学染色反应，快速、简单地检测与医学相关的各种功能化 SPION 是可能的。该方案可应用于经过最少预处理的生物样品（例如全血、血浆或血清、细胞悬浮液、活检、组织学制备等），并且通常不需要复杂的信号放大系统。使用 SPION 标记的化合物还有助于降低诊断和患者护理的成本。
