Near-Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid

Angew Chem Int Ed Engl. 2018 Jan 26;57(5):1256-1260. doi: 10.1002/anie.201710727. Epub 2018 Jan 5.

Abstract

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.

Keywords: fibroblast activation protein-alpha; molecular probes; near-infrared fluorescence imaging; skin diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Endopeptidases
  • Fluorescent Dyes / chemistry*
  • Gelatinases / genetics
  • Gelatinases / metabolism
  • Humans
  • In Vitro Techniques
  • Keloid / metabolism
  • Keloid / pathology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Fluorescence
  • Models, Biological
  • Peptides / chemistry
  • Peptides / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Spectroscopy, Near-Infrared
  • Substrate Specificity

Substances

  • Fluorescent Dyes
  • Membrane Proteins
  • Peptides
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases