Open AccessCyclodextrin-Based Peptide Self-Assemblies (Spds) That Enhance Peptide-Based Fluorescence Imaging and Antimicrobial Efficacy
Author(s) -
Jinbiao Jiao,
Guanzhen Wang,
XiLe Hu,
Yi Zang,
Stéphane Maisonneuve,
Adam Sedgwick,
Jonathan L. Sessler,
Juan Xie,
Jia Li,
XiaoPeng He,
He Tian
Publication year - 2019
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.9b11207
Subject(s) - chemistry , peptide , supramolecular chemistry , antimicrobial , fluorescence , cyclodextrin , biophysics , intracellular , combinatorial chemistry , nanotechnology , biochemistry , biology , organic chemistry , physics , materials science , quantum mechanics , crystal structure
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-4 H -pyran appended β-cyclodextrin ( DCM 7 -β-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 DCM 7 -β-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.