Department of Applied Chemistry, Key Laboratory of Space Applied Physics and Chemistry of Ministry of Education, School of Natural and Applied Science, Northwestern Polytechnical University, Xi'an 710072, China.
Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Int J Biol Macromol. 2020 Jun 15;153:723-735. doi: 10.1016/j.ijbiomac.2020.03.061. Epub 2020 Mar 10.
Lysozyme amyloid fibrils, the misfolding structures generated from natural state of lysozyme, are found to be related with non-neuropathic systemic amyloidosis. Therefore, inhibiting the formation of amyloid and disaggregating amyloid fibers are both effective strategies. Herein, we present a combination of Epigallocatechin-3-gallate (EGCG), imprinting technology and magnetic nanoparticles to obtain a kind of promising nanomaterials (MINs@EGCG) for amyloid inhibition, drug carrier and facile separation triple functions. We declared the efficacy of MINs@EGCG from two perspectives. For inhibition, Circular dichroism (CD) spectrum illustrated that the miss transition from α-helix structure to β-sheet could be blocked by MINs@EGCG, and the inhibition efficiency was higher than 80%. These results were further verified by Thioflavin T (ThT) analysis. For disaggregation and cleansing, the helical and highly periodic structure of amyloid fibrils could be converted into their counterparts by MINs@EGCG. Furthermore, with the aid of external magnetic field, the cleansing efficiency of counterparts-MINs@EGCG complex was up to 80%. Most importantly, bio-related experiments showed superior biocompatibility and anti-amyloid fibrils toxicity of MINs@EGCG, indicating the great potential of our system to work as an effective amyloidosis therapy platform.
溶菌酶淀粉样纤维是由溶菌酶天然状态下错误折叠形成的结构，与非神经病变系统性淀粉样变性有关。因此，抑制淀粉样形成和解聚淀粉样纤维都是有效的策略。在此，我们结合没食子儿茶素没食子酸酯（EGCG）、印迹技术和磁性纳米粒子，获得了一种具有应用前景的纳米材料（MINs@EGCG），可用于抑制淀粉样、载药和易于分离等三重功能。我们从两个方面说明了 MINs@EGCG 的功效。在抑制方面，圆二色性（CD）谱表明 MINs@EGCG 可以阻止从α-螺旋结构向β-折叠的错误转变，抑制效率高于 80%。这些结果通过噻唑蓝（ThT）分析得到了进一步验证。在解聚和清除方面，淀粉样纤维的螺旋和高度周期性结构可以通过 MINs@EGCG 转化为其对应物。此外，在外加磁场的帮助下，对应物-MINs@EGCG 复合物的清除效率高达 80%。最重要的是，生物相关实验表明 MINs@EGCG 具有优异的生物相容性和抗淀粉样纤维毒性，表明我们的系统有很大的潜力作为一种有效的淀粉样变性治疗平台。
