State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, P. R. China.
J Mater Chem B. 2019 Mar 7;7(9):1397-1403. doi: 10.1039/c8tb02964d. Epub 2019 Jan 21.
Amyloid fibrillation of proteins is likely a key factor leading to the development of amyloidosis-associated diseases. Inhibiting amyloid fibrillation has become a crucial therapeutic strategy. Water-soluble, fluorescent silicon nanoparticles (SiNPs) have great potential in biomedicine for various therapeutic and diagnostic purposes; however, it is unclear whether SiNPs have the ability to inhibit amyloid fibrillation. Herein, insulin was chosen as a protein model, and SiNPs of varying sizes were synthesized upon UV irradiation. The influence of size and concentration of the SiNPs on insulin fibrillation was investigated, and it has been observed that these variables were crucial in regulating insulin fibrillation. Using an average particle size of 6.6 nm and increasing the concentration of the SiNPs to 5.0 μg mL, the Thioflavin T (ThT) fluorescence intensity decreased significantly by 90%, with an increased lag time of 76.8 h, compared to that of the control. Insulin aggregates were short, thin fibrils or clusters when incubated with SiNPs, compared to the long, thick fibrils formed for insulin alone. Additionally, we found that the SiNPs prevent the conformational transition of insulin from its initial structure to β-sheets, and thus inhibit nucleation, which is necessary for the formation of large fibrils. The inhibitory activity is attributed to the interactions between the SiNPs and insulin during the nucleation period. Our results demonstrate that the SiNPs disrupt insulin amyloid fibrillation, and thus, may play a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.
蛋白质的淀粉样纤维形成很可能是导致淀粉样变性相关疾病发展的关键因素。抑制淀粉样纤维形成已成为一种重要的治疗策略。水溶性、荧光硅纳米颗粒（SiNPs）在各种治疗和诊断目的的生物医学中具有巨大的潜力；然而，目前尚不清楚 SiNPs 是否具有抑制淀粉样纤维形成的能力。在此，选择胰岛素作为蛋白质模型，并通过紫外线照射合成了不同尺寸的 SiNPs。研究了 SiNPs 的尺寸和浓度对胰岛素纤维形成的影响，结果表明这些变量在调节胰岛素纤维形成中起着至关重要的作用。使用平均粒径为 6.6nm 并将 SiNPs 的浓度增加到 5.0μg/mL 时，与对照相比，Thioflavin T（ThT）荧光强度显著降低了 90%，同时延滞时间增加到 76.8h。与单独孵育胰岛素相比，当与 SiNPs 孵育时，胰岛素聚集体是短而细的纤维或簇，而不是单独孵育胰岛素形成的长而厚的纤维。此外，我们发现 SiNPs 阻止胰岛素从初始结构向β-折叠的构象转变，从而抑制核形成，核形成是形成大纤维所必需的。这种抑制活性归因于在成核期 SiNPs 与胰岛素之间的相互作用。我们的结果表明，SiNPs 破坏了胰岛素的淀粉样纤维形成，因此可能在淀粉样相关疾病的新治疗和诊断策略中发挥有用的作用。
