Nanoparticles with Ampholytic Surfaces for Binding and Disintegration of Amyloid Fibrils

IF 10.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Suman Mandal, Minh Dang Nguyen, Nikhil Ranjan Jana* and T. Randall Lee*, 
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引用次数: 0

Abstract

Amyloid fibrils and associated protein aggregates are key contributors to a range of neurodegenerative diseases. Recent studies suggest that nanoparticles with tailored surface chemistries can effectively bind to and disrupt these fibrils. Here, we investigate the role of nanoparticle surface charge in mediating interactions with amyloid fibrils and promoting their disintegration. We synthesized seven types of charged iron oxide nanoparticles (cationic, anionic, and ampholytic) in colloidal form with hydrodynamic diameters ranging from 15 to 40 nm. Interaction studies with mature lysozyme fibrils revealed that ampholytic nanoparticles exhibited the highest binding affinity among the tested surface types. This enhanced affinity is attributed to reduced nonspecific interactions and favorable electrostatic compatibility. Ampholytic nanoparticles disrupted mature amyloid fibrils approximately 2.5 times more effectively than other surface-charged nanoparticles, leading to smaller fibril fragments via mechanical agitation. We further show that agitation-induced mechanical force, along with piezocatalytically generated reactive oxygen species (ROS), contributes to fibril degradation. These findings highlight the critical role of ampholytic surface charge in promoting fibril disintegration and suggest that such nanoparticles could be leveraged in therapeutic strategies for neurodegenerative diseases involving amyloid aggregation.

Ampholytic nanoparticles bind and disintegrate amyloid fibrils efficiently via electrostatic interactions and ROS generation under agitation; cationic and anionic types are less effective.

具有两性溶解表面的纳米颗粒用于淀粉样蛋白原纤维的结合和解体。
淀粉样蛋白原纤维和相关蛋白聚集体是一系列神经退行性疾病的关键因素。最近的研究表明,具有特定表面化学成分的纳米颗粒可以有效地结合并破坏这些原纤维。在这里,我们研究了纳米颗粒表面电荷在介导淀粉样蛋白原纤维相互作用和促进其解体中的作用。我们合成了7种带电荷的氧化铁纳米颗粒(阳离子、阴离子和两性离子),它们以胶体形式存在,水动力直径从15到40纳米不等。与成熟溶菌酶原纤维的相互作用研究表明,两性溶解纳米颗粒在被测表面类型中具有最高的结合亲和力。这种增强的亲和力归因于减少的非特异性相互作用和良好的静电相容性。两性溶解纳米颗粒破坏成熟淀粉样蛋白原纤维的效率是其他表面带电纳米颗粒的约2.5倍,通过机械搅拌导致更小的纤维碎片。我们进一步表明,搅拌诱导的机械力,以及压电催化产生的活性氧(ROS),有助于纤维降解。这些发现突出了两性表面电荷在促进纤维分解中的关键作用,并表明这种纳米颗粒可用于涉及淀粉样蛋白聚集的神经退行性疾病的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Central Science
ACS Central Science Chemical Engineering-General Chemical Engineering
CiteScore
25.50
自引率
0.50%
发文量
194
审稿时长
10 weeks
期刊介绍: ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.
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