Gold Nanoparticles with Adaptable Self-Assembled Monolayer Shells Allow Multivalent Inhibition and Sensing of Influenza Virus at Ultralow Concentrations

IF 10.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yulia Sergeeva*, , , Sing Yee Yeung, , , Thomas Hix-Janssens, , and , Börje Sellergren*, 
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引用次数: 0

Abstract

Multivalent inhibitors that mimic the polysaccharide array on cells represent a new paradigm in the development of antiviral agents and antibiotics. Covalent ligand anchoring limits the affinity and, in turn, potency of these inhibitors with dissociation constants (Kd) commonly found in the micromolar or upper nanomolar range. Addressing this deficiency we here report on easily accessible gold core–shell nanoparticles (rSAM-NPs) featuring adaptable reversible self-assembled monolayer (rSAM)-based shells. The rSAMs are anchored by noncovalent amidinium-carboxylate interactions on gold nanoparticles at slightly alkaline pH resulting in laterally mobile pH-responsive assemblies that are functional at physiological pH. Introducing sialic acid ligands in the shell, we show that the rSAM-NPs strongly interact with the influenza virus surface protein hemagglutinin (limit of detection LoD < 2 nM) and deactivated bird flu virus H5N1 (LoD < 1 HAU) in allantoic liquid. Finally, we show that the rSAM-NPs effectively inhibit the interaction of the virus with red blood cells at concentrations in the low picomolar range. This represents a significant increase in potency with respect to multivalent inhibitors of similar size based on covalently anchored monosaccharides.

Gold core nanoparticles with adaptable, sialic acid presenting, self-assembled monolayer shells effectively inhibit the interaction between deactivated bird flu virus (H5N1) and red blood cells at low picomolar concentrations.

具有适应性自组装单层壳的金纳米颗粒允许在超低浓度下对流感病毒进行多价抑制和感应
模拟细胞上多糖阵列的多价抑制剂代表了抗病毒药物和抗生素开发的新范式。共价配体锚定限制了这些解离常数(Kd)通常在微摩尔或上纳摩尔范围内的抑制剂的亲和力和效力。为了解决这一缺陷,我们在这里报道了一种易于获取的金核壳纳米粒子(rSAM- nps),它具有适应性强、可逆的自组装单层(rSAM)壳。rSAMs通过非共价氨基羧酸相互作用锚定在微碱性的金纳米颗粒上,从而形成在生理pH下具有功能的横向移动的pH响应组装体。在外壳中引入唾液酸配体,我们发现rSAMs - nps与流感病毒表面蛋白血凝素(检测限为2 nM)和尿囊液中灭活的H5N1禽流感病毒(检测限为1 HAU)有强烈的相互作用。最后,我们发现rSAM-NPs在低皮摩尔浓度范围内有效抑制病毒与红细胞的相互作用。这表明相对于基于共价锚定单糖的类似大小的多价抑制剂,效力显著增加。具有适应性强、唾液酸呈状、自组装单层壳的金核纳米颗粒在低皮摩尔浓度下有效抑制灭活禽流感病毒(H5N1)与红细胞之间的相互作用。
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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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