Department of Chemical Engineering, National Taiwan University, Taipei, 10617, Taiwan.
Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 10617, Taiwan.
Colloids Surf B Biointerfaces. 2018 Dec 1;172:674-683. doi: 10.1016/j.colsurfb.2018.09.029. Epub 2018 Sep 14.
More than thirty human proteins and/or peptides can aggregate to form amyloid deposits that are linked to several amyloid diseases including clinical syndrome injection-localized amyloidosis, which is correlated with the aggregation of the 51-residue polypeptide insulin. While no cure is currently available toward tackling amyloid diseases, prevention or suppression of amyloid fibrillization is considered as the primary therapeutic strategy. Nanomaterials have been demonstrated to possess great potential in the fields of biomedical diagnosis and drug delivery, they are also able to affect the amyloid aggregation of proteins. This work explores the effects of three different magnetic nanoparticles coated with dextran-based polymers on the in vitro amyloid fibrillogenesis of human insulin. Surface modification of nanoparticles with dextran-based polymers was used to improve the biocompatibility of maghemite nanoparticles. We demonstrated that insulin fibrillization may be mitigated by the studied nanoparticles in a concentration-dependent fashion as verified by ThT binding assay and transmission electron microscopy. The extent of inhibitory activity against human insulin fibril formation was found to be associated with the physico-chemical properties of nanoparticles, with the highest inhibitory activity observed for diethylaminoethyl-dextran-coated nanoparticles. Using circular dichroism spectroscopy, ANS fluorescence spectroscopy, and right-angle light scattering, we probed the structural/conformational changes and investigated the aggregating behavior of insulin upon treatment with nanoparticles. This work demonstrates that nanoparticles with an appropriate surface modification can be utilized to suppress or even inhibit amyloid fibril formation of proteins.
三十多种人类蛋白质和/或肽可以聚集形成淀粉样沉积物，这些沉积物与几种淀粉样疾病有关，包括临床综合征局部淀粉样变性，这与 51 个残基多肽胰岛素的聚集有关。虽然目前尚无针对淀粉样疾病的治疗方法，但预防或抑制淀粉样纤维形成被认为是主要的治疗策略。纳米材料在生物医学诊断和药物输送领域具有巨大的潜力，它们也能够影响蛋白质的淀粉样聚集。这项工作探讨了三种不同的葡聚糖基聚合物包覆的磁性纳米粒子对人胰岛素体外淀粉样纤维形成的影响。用葡聚糖基聚合物对纳米粒子进行表面修饰，以提高磁赤铁矿纳米粒子的生物相容性。我们通过 ThT 结合试验和透射电子显微镜证明，胰岛素纤维化可能被研究的纳米粒子以浓度依赖的方式减轻。对人胰岛素纤维形成的抑制活性的程度与纳米粒子的物理化学性质有关，其中二乙氨基乙基-葡聚糖包覆的纳米粒子具有最高的抑制活性。通过圆二色性光谱、ANS 荧光光谱和直角光散射，我们探测了胰岛素在纳米粒子处理下的结构/构象变化和聚集行为。这项工作表明，具有适当表面修饰的纳米粒子可用于抑制甚至抑制蛋白质的淀粉样纤维形成。
