Design of Fluorinated Peptides as Biotransformed Urinalysis Biomarkers for Non-Invasive Diagnosis and Treatment of Liver Injury through Enzyme Directed Kinetics

IF 27.4 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Ruxin Feng, Weilu Xu, Jinhui Ning, Qian Ma, Hui Wang, Liangyu Li, Suying Xu, Leyu Wang
{"title":"Design of Fluorinated Peptides as Biotransformed Urinalysis Biomarkers for Non-Invasive Diagnosis and Treatment of Liver Injury through Enzyme Directed Kinetics","authors":"Ruxin Feng,&nbsp;Weilu Xu,&nbsp;Jinhui Ning,&nbsp;Qian Ma,&nbsp;Hui Wang,&nbsp;Liangyu Li,&nbsp;Suying Xu,&nbsp;Leyu Wang","doi":"10.1002/adma.202413571","DOIUrl":null,"url":null,"abstract":"<p>Urinalysis, as a non-invasive and efficient diagnostic method, is very important but faces great challenges due to the complex compositions of urine and limited naturally occurring biomarkers for diseases. Herein, by leveraging the intrinsic absence of endogenous fluorinated interference, a strategy with the enzymatically activated assembly of synthetic fluorinated peptide for cholestatic liver injury (CLI) diagnosis and treatment through <sup>19</sup>F nuclear magnetic resonance (NMR) urinalysis and efficient drug retention is developed. Specifically, alkaline phosphatase (ALP), overexpressed in the liver of CLI mice, triggers the assembly of fluorinated peptide, thus, directing the traffic and dynamic distribution of the synthetic biomarkers after administration, whereas CLI mice display much slower clearance of peptides through urine as compared with healthy counterparts. As such, it enables to transform pathophysiological information into exogenous signals via noninvasive urinary monitoring. Moreover, as a proof-of-concept, by grafting different functional groups to peptides, the theranostic platforms can be established to provide a new paradigm for the design of multifunctional peptides.</p>","PeriodicalId":114,"journal":{"name":"Advanced Materials","volume":"37 8","pages":""},"PeriodicalIF":27.4000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Materials","FirstCategoryId":"88","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/adma.202413571","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

Urinalysis, as a non-invasive and efficient diagnostic method, is very important but faces great challenges due to the complex compositions of urine and limited naturally occurring biomarkers for diseases. Herein, by leveraging the intrinsic absence of endogenous fluorinated interference, a strategy with the enzymatically activated assembly of synthetic fluorinated peptide for cholestatic liver injury (CLI) diagnosis and treatment through 19F nuclear magnetic resonance (NMR) urinalysis and efficient drug retention is developed. Specifically, alkaline phosphatase (ALP), overexpressed in the liver of CLI mice, triggers the assembly of fluorinated peptide, thus, directing the traffic and dynamic distribution of the synthetic biomarkers after administration, whereas CLI mice display much slower clearance of peptides through urine as compared with healthy counterparts. As such, it enables to transform pathophysiological information into exogenous signals via noninvasive urinary monitoring. Moreover, as a proof-of-concept, by grafting different functional groups to peptides, the theranostic platforms can be established to provide a new paradigm for the design of multifunctional peptides.

Abstract Image

利用酶导向动力学设计氟化肽作为无创诊断和治疗肝损伤的生物转化尿液分析生物标志物
尿液分析作为一种无创、高效的诊断方法,具有重要的意义,但由于尿液成分复杂,自然存在的疾病生物标志物有限,因此面临着很大的挑战。本研究利用内源性氟化干扰的内在缺位,通过19F核磁共振(NMR)尿液分析和有效的药物保留,开发了一种酶激活合成氟化肽组装用于胆汁淤积性肝损伤(CLI)诊断和治疗的策略。具体来说,碱性磷酸酶(ALP)在CLI小鼠的肝脏中过度表达,触发了氟化肽的组装,从而指导了给药后合成生物标志物的传输和动态分布,而CLI小鼠通过尿液清除肽的速度比健康小鼠慢得多。因此,它可以通过无创尿液监测将病理生理信息转化为外源性信号。此外,作为概念验证,通过将不同的官能团嫁接到多肽上,可以建立治疗平台,为多功能肽的设计提供新的范例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信