Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons.
Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons.
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DOI：
10.1002/smll.201802825
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Ke PC
中科院分区：
文献类型：
--
作者：
Faridi A;Sun Y;Okazaki Y;Peng G;Gao J;Kakinen A;Faridi P;Zhao M;Javed I;Purcell AW;Davis TP;Lin S;Oda R;Ding F;Ke PC
淀粉样蛋白原纤维通常显示手性，这是一种在淀粉样蛋白疾病的治疗方法的开发中很少被利用的特征。在这里，我们报告，第一次，使用介观手性二氧化硅纳米带对人体胰岛淀粉样多肽（IAPP），其聚集的肽在2型糖尿病中有牵连的体内淀粉样变性。我们的硫磺素T测定和透射电子显微镜显示通过消除成核相和缩短由纳米结构的伸长相加速IAPP的絮凝。粗粒度的模拟提供了补充分子的见解，通过其非特异性结合和定向播种的纳米结构的淀粉样蛋白聚集的加速。这种加速的IAPP过滤转化为降低的毒性，特别是对于右手二氧化硅纳米带，如通过细胞活力、氦离子显微镜以及斑马鱼胚胎存活、发育和行为测定所揭示的。这项研究暗示了利用手性纳米技术对抗淀粉样蛋白介观对映体选择性及其相关疾病的潜力。二氧化硅纳米带在胚胎斑马鱼模型中拯救了反手淀粉样蛋白IAPP的毒性，指出了利用纳米级手性对抗淀粉样蛋白生成的潜力。
Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. Here we report, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. Our thioflavin T assay and transmission electron microscopy showed accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offered complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases. Silica nanoribbons rescued the toxicity of oppositely-handed amyloid protein IAPP in an embryonic zebrafish model, pointing to the potential of exploiting nanoscale chirality against amyloidogenesis.
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影响因子：
4.3
作者：
Auer S;Trovato A;Vendruscolo M
通讯作者：
Vendruscolo M
影响因子：
5.6
作者：
Ding, Feng;Furukawa, Yoshiaki;Nukina, Nobuyuki;Dokholyan, Nikolay V.
通讯作者：
Dokholyan, Nikolay V.
影响因子：
4.3
作者：
Delgado-Perez, Teresa;Bouchet, Lydia M.;Perez-Prieto, Julia
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Perez-Prieto, Julia
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5.2
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Ichinose, Wataru;Miyagawa, Masamichi;Yamaguchi, Masahiko
通讯作者：
Yamaguchi, Masahiko
影响因子：
13.8
作者：
Kalueff, Allan V.;Stewart, Adam Michael;Gerlai, Robert
通讯作者：
Gerlai, Robert