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单站点铁锚定淀粉样蛋白水凝胶作为酒精解毒的催化平台。

Single-site iron-anchored amyloid hydrogels as catalytic platforms for alcohol detoxification.

机构信息

Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.

Particle and Interfacial Technology Group, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.

出版信息

Nat Nanotechnol. 2024 Aug;19(8):1168-1177. doi: 10.1038/s41565-024-01657-7. Epub 2024 May 13.

Abstract

Constructing effective antidotes to reduce global health impacts induced by alcohol prevalence is a challenging topic. Despite the positive effects observed with intravenous applications of natural enzyme complexes, their insufficient activities and complicated usage often result in the accumulation of toxic acetaldehyde, which raises important clinical concerns, highlighting the pressing need for stable oral strategies. Here we present an effective solution for alcohol detoxification by employing a biomimetic-nanozyme amyloid hydrogel as an orally administered catalytic platform. We exploit amyloid fibrils derived from β-lactoglobulin, a readily accessible milk protein that is rich in coordinable nitrogen atoms, as a nanocarrier to stabilize atomically dispersed iron (ferrous-dominated). By emulating the coordination structure of the horseradish peroxidase enzyme, the single-site iron nanozyme demonstrates the capability to selectively catalyse alcohol oxidation into acetic acid, as opposed to the more toxic acetaldehyde. Administering the gelatinous nanozyme to mice suffering from alcohol intoxication significantly reduced their blood-alcohol levels (decreased by 55.8% 300 min post-alcohol intake) without causing additional acetaldehyde build-up. Our hydrogel further demonstrates a protective effect on the liver, while simultaneously mitigating intestinal damage and dysbiosis associated with chronic alcohol consumption, introducing a promising strategy in effective alcohol detoxification.

摘要

构建有效的解毒剂以减少由酒精流行引起的全球健康影响是一个具有挑战性的话题。尽管静脉内应用天然酶复合物观察到了积极的效果,但它们的活性不足和复杂的使用方式常常导致有毒的乙醛积累,这引起了重要的临床关注,凸显了对稳定口服策略的迫切需求。在这里,我们提出了一种通过使用仿生纳米酶淀粉样纤维水凝胶作为口服催化平台来进行酒精解毒的有效方法。我们利用β-乳球蛋白衍生的淀粉样纤维,这是一种丰富的配位氮原子的易得的牛奶蛋白,作为纳米载体来稳定原子分散的铁(以亚铁为主)。通过模拟辣根过氧化物酶酶的配位结构,单原子铁纳米酶能够选择性地催化酒精氧化为乙酸,而不是更有毒的乙醛。将凝胶状纳米酶施用于酒精中毒的小鼠,可显著降低其血液中的酒精水平(在摄入酒精 300 分钟后降低了 55.8%),而不会导致额外的乙醛积累。我们的水凝胶还对肝脏具有保护作用,同时减轻与慢性酒精摄入相关的肠道损伤和菌群失调,为有效的酒精解毒提供了一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c20/11329373/70ad781c251c/41565_2024_1657_Fig1_HTML.jpg

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