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Cyclodextrin-Based Peptide Self-Assemblies (Spds) That Enhance Peptide-Based Fluorescence Imaging and Antimicrobial Efficacy.


ABSTRACT: 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 β-cyclodextrin (DCM7-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 DCM7-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.

SUBMITTER: Jiao JB 

PROVIDER: S-EPMC8009276 | biostudies-literature |

REPOSITORIES: biostudies-literature

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