title: A near-IR uncaging strategy based on cyanine photochemistry.
abstract: 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.
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute , 376 Boyles Street, Frederick, Maryland 21702, United States.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Gorka
authors.forename: Roger R
authors.initials: RR
authors.lastname: Nani
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zhu
authors.forename: Susan
authors.initials: S
authors.lastname: Mackem
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schnermann
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D015195:Drug Design; D065171:Estrogen Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007259:Infrared Rays; D008024:Ligands; D061986:MCF-7 Cells; D051379:Mice; D019800:Phenol / Q000737:chemistry; D055668:Photochemical Processes
chemical_list: D002232:Carbocyanines; D004337:Drug Carriers; D065171:Estrogen Receptor Antagonists; D008024:Ligands; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019800:Phenol