文献类型：期刊文献

英文题名：Cyclodextrin-Based Peptide Self-Assemblies (Spds) That Enhance Peptide-Based Fluorescence Imaging and Antimicrobial Efficacy

作者：Jiao, Jin-Biao[2,6];Wang, Guan-Zhen[3,4];Hu, Xi-Le[6];Zang, Yi[3];Maisonneuve, Stephane[2];Sedgwick, Adam C.[1];Sessler, Jonathan L.[1];Xie, Juan[2];Li, Jia[3,4,5];He, Xiao-Peng[6];Tian, He[6]

机构：[1]Univ Texas Austin, Dept Chem, 105 East 24th St A5300, Austin, TX 78712 USA;[2]Univ Paris Saclay, ENS Paris Saclay, CNRS, PPSM, 61 Av President Wilson, F-94235 Cachan, France;[3]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, 189 Guo Shoujing Rd, Shanghai 201203, Peoples R China;[4]Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;[5]Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, 1 Wenhai Rd, Qingdao 266237, Peoples R China;[6]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Key Lab Adv Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2020

卷号：142

期号：4

起止页码：1925

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20200508105133);WOS:【SCI-EXPANDED(收录号:WOS:000510531900039)】；

基金：The authors thank the National Natural Science Foundation of China (Nos. 21788102, 91853201, 21722801, 81673489, and 31871414), the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03), the International Cooperation Program of Shanghai Science and Technology Committee (No. 17520750100) and the Fundamental Research Funds for the Central Universities (222201717003) for financial support. The work in France was supported by the COST Action Functional Glyconanomaterials for the Development of Diagnostics and Targeted Therapeutic Probes (CA18132). The work in Austin was supported by the National Institutes of Health (GM RO1 103790 to J.L.S.) and the Robert A. Welch Foundation (F-0018).

语种：英文

外文关键词：Probes - Escherichia coli - Supramolecular chemistry - Cell death - Fluorescence imaging - Cyclodextrins

摘要：As a result of their high specificity for their corresponding biological targets, peptides have shown significant potential in a range of diagnostic and therapeutic applications. However, their widespread use has been limited by their minimal cell permeability and stability in biological milieus. We describe here a hepta-dicyanomethylene-4H-pyran appended beta-cyclodextrin (DCM7-beta-CD) that acts as a delivery enhancing "host" for 1-bromonaphthalene-modified peptides, as demonstrated with peptide probes P1-P4. Interaction between the fluorescent peptides P1-P3 and DCM7-beta-CD results in the hierarchical formation of unique supramolecular architectures, which we term supramolecular-peptide-dots (Spds). Each Spd (Spd-1, Spd-2, and Spd-3) was found to facilitate the intracellular delivery of the constituent fluorescent probes (P1-P3), thus allowing spatiotemporal imaging of an apoptosis biomarker (caspase-3) and mitosis. Spd-4, incorporating the antimicrobial peptide P4, was found to provide an enhanced therapeutic benefit against both Gram-positive and Gram-negative bacteria relative to P4 alone. In addition, a fluorescent Spd-4 was prepared, which revealed greater bacterial cellular uptake compared to the peptide alone (P4-FITC) in E. coli. (ATCC 25922) and S. aureus (ATCC 25923). This latter observation supports the suggestion that the Spd platform reported here has the ability to facilitate the delivery of a therapeutic peptide and provides an easy-to-implement strategy for enhancing the antimicrobial efficacy of known therapeutic peptides. The present findings thus serve to highlight a new and effective supramolecular delivery approach that is potentially generalizable to overcome limitations associated with functional peptides.