Laboratory of Inorganic Chemistry, Department of Chemistry , Aristotle University of Thessaloniki , Thessaloniki , 54124 Greece.
ACS Chem Neurosci. 2019 Aug 21;10(8):3796-3804. doi: 10.1021/acschemneuro.9b00292. Epub 2019 Jul 25.
Amyloidosis, the aggregation of naturally soluble proteins into fibrils, is the main pathological hallmark of central nervous system (CNS) disorders, and new therapeutic approaches can be introduced through nanotechnology. Herein, magnetic nanoparticles (MNPs) are proposed to combat amyloidosis and act as CNS theranostic (therapy and diagnosis) candidates through magnetomechanical forces that can be induced under a low-frequency magnetic field. In that vein, a modified one-step microwave-assisted polyol process has been employed to synthesize hybrid organic/inorganic zinc ferrite (ZnFeO) MNPs with different levels of zinc doping (0.30 < < 0.6) derived from the utilized polyol. The lowest doped ( = 0.30) MNPs exhibited high magnetization (127 emu/g), high imaging ability ( = 432 mM s), and relatively small hydrodynamic size (180 nm), decisive characteristics to further evaluate their CNS theranostic potential. Their effect on the fibrillation/degradation was monitored in two model proteins, insulin and albumin, in the presence/absence of variant external magnetic fields (static, rotating, or alternating) via Thioflavin T (ThT) fluorescence assay and optical fluorescence microscopy. The MNPs were injected either in oligomer solution where significant fibrillation delay was observed, boosted by zinc ionic leaching of MNPs, or in already formed amyloid plaques where up to 86% amyloid degradation was recorded in the presence of magnetic fields, unveiling magnetomechanical antifibrillation properties. The alternating magnetic field (4 Hz) allows the bouncing of the MNPs into the amyloid net driven by the magnetic forces, and thus is featured as the preferred "dancing mode", which strengthens the degrading efficacy of MNPs.
淀粉样变性，即天然可溶性蛋白质聚集成纤维，是中枢神经系统 (CNS) 疾病的主要病理标志，通过纳米技术可以引入新的治疗方法。在此，提出了磁性纳米颗粒 (MNP)，通过低频磁场下可诱导的磁机械力来对抗淀粉样变性，并作为 CNS 治疗诊断 (治疗和诊断) 候选物。为此，采用改进的一步微波辅助多元醇法合成了不同锌掺杂水平 (0.30 < < 0.6) 的有机/无机锌铁氧体 (ZnFeO) 杂化 MNP，该多元醇来源于所使用的多元醇。最低掺杂 ( = 0.30) 的 MNP 表现出高磁化强度 (127 emu/g)、高成像能力 ( = 432 mM s) 和相对较小的水动力尺寸 (180 nm)，这些特性对进一步评估其 CNS 治疗诊断潜力至关重要。通过噻唑蓝 (ThT) 荧光法和光学荧光显微镜，在存在/不存在不同外加磁场 (静态、旋转或交变) 的情况下，监测了这些 MNP 对两种模型蛋白胰岛素和白蛋白的纤维化/降解的影响。将 MNP 注射到寡聚物溶液中，观察到明显的纤维化延迟，这是由于 MNP 的锌离子浸出所致，或者注射到已经形成的淀粉样斑块中，在磁场存在的情况下，记录到高达 86%的淀粉样降解，显示出磁机械抗纤维化特性。交变磁场 (4 Hz) 允许 MNP 在磁场的驱动下在淀粉样纤维网中反弹，因此被认为是首选的“跳动模式”，这增强了 MNP 的降解效果。
