國家衛生研究院 NHRI:Item 3990099045/11112
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    題名: Subnanometer gold clusters adhere to lipid a for protection against endotoxin-induced sepsis
    作者: Liao, FH;Wu, TH;Huang, YT;Lin, WJ;Su, CJ;Jeng, US;Kuo, SC;Lin, SY
    貢獻者: Institute of Biomedical Engineering and Nanomedicine;Immunology Research Center;National Institute of Infectious Diseases and Vaccinology
    摘要: Endotoxicity originating from a dangerous debris (i.e., lipopolysaccharide, LPS) of Gram-negative bacteria is a challenging clinical problem, but no drugs or therapeutic strategies that can successfully address this issue have been identified yet. In this study, we report a subnanometer gold cluster that can efficiently block endotoxin activity to protect against sepsis. The endotoxin blocker consists of a gold nanocluster that serves as a flakelike substrate and a coating of short alkyl motifs that act as an adhesive to dock with LPS by compacting the intramolecular hydrocarbon chain-chain distance ( d-spacing) of lipid A, an endotoxicity active site that can cause overwhelming cytokine induction resulting in sepsis progression. Direct evidence showed the d-spacing values of lipid A to be decreased from 4.19 A to either 3.85 or 3.54 A, indicating more dense packing densities in the presence of subnanometer gold clusters. In terms of biological relevance, the concentrations of key pro-inflammatory NF-kappaB-dependent cytokines, including plasma TNF-alpha, IL-6, and IL-1beta, and CXC chemokines, in LPS-challenged mice showed a noticeable decrease. More importantly, we demonstrated that the treatment of antiendotoxin gold nanoclusters significantly prolonged the survival time in LPS-induced septic mice. The ultrasmall gold nanoclusters could target lipid A of LPS to deactivate endotoxicity by compacting its packing density, which might constitute a potential therapeutic strategy for the early prevention of sepsis caused by Gram-negative bacterial infection.
    日期: 2018-05
    關聯: Nano Letters. 2018 May;18(5):2864-2869.
    Link to: http://dx.doi.org/10.1021/acs.nanolett.7b05464
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1530-6984&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000432093200018
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85046627561
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