A near-IR uncaging strategy based on cyanine photochemistry

J Am Chem Soc. 2014 Oct 8;136(40):14153-9. doi: 10.1021/ja5065203. Epub 2014 Sep 24.


The development of photocaging groups activated by near-IR light would enable new approaches for basic research and allow for spatial and temporal control of drug delivery. Here we report a near-IR light-initiated uncaging reaction sequence based on readily synthesized C4'-dialkylamine-substituted heptamethine cyanines. Phenol-containing small molecules are uncaged through sequential release of the C4'-amine and intramolecular cyclization. The release sequence is initiated by a previously unexploited photochemical reaction of the cyanine fluorophore scaffold. The uncaging process is compatible with biological milieu and is initiated with low intensity 690 nm light. We show that cell viability can be inhibited through light-dependent release of the estrogen receptor antagonist, 4-hydroxycyclofen. In addition, through uncaging of the same compound, gene expression is controlled with near-IR light in a ligand-dependent CreER(T)/LoxP-reporter cell line derived from transgenic mice. These studies provide a chemical foundation that we expect will enable specific delivery of small molecules using cytocompatible, tissue penetrant near-IR light.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Carbocyanines / chemical synthesis
  • Carbocyanines / chemistry*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Design
  • Estrogen Receptor Antagonists / chemistry
  • Estrogen Receptor Antagonists / pharmacology
  • Green Fluorescent Proteins / genetics
  • Humans
  • Infrared Rays*
  • Ligands
  • MCF-7 Cells
  • Mice
  • Phenol / chemistry
  • Photochemical Processes*


  • Carbocyanines
  • Drug Carriers
  • Estrogen Receptor Antagonists
  • Ligands
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Phenol