title: Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents.
abstract: A strategy for the light-activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is described. We have found that membrane-permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid-enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes. Subsequent illumination drives the secretion of the bioactive species from red blood cells. Photorelease is triggered by wavelengths in the red, far-red, and near-IR regions, which can be pre-assigned by affixing a fluorophore with the desired excitation wavelength to the Cbl-bioagent conjugate. Pre-assigned wavelengths allow different biologically active compounds to be specifically and unambiguously photoreleased from common carriers.
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Current address: Department of Chemistry, 300 Science & Technology Building, East Carolina University, Greenville, NC, 27858, USA.
authors.forename: Robert M
authors.identifier: 0000-0002-4465-4212
authors.initials: RM
authors.lastname: Hughes
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marvin
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Current address: Center for Nanotechnology in Drug Delivery, Department of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Rodgers
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Current address: KBI Biopharma, 1101 Hamlin Rd, Durham, NC, 27704, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Oien
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Current address: Skaggs School of Pharmacy, University of Colorado, 12850 E. Montview Blvd, Aurora, CO, 80045, USA.
authors.forename: Weston J
authors.initials: WJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: David S
authors.identifier: 0000-0002-0901-1617
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D001896:Boron Compounds / Q000737:chemistry* / Q000378:metabolism; D003078:Colchicine / Q000737:chemistry* / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008727:Methotrexate / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism; D055668:Photochemical Processes; D014805:Vitamin B 12 / Q000737:chemistry* / Q000378:metabolism
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D014805:Vitamin B 12; D017239:Paclitaxel; D003078:Colchicine; D008727:Methotrexate
keywords: cobalamines; drug delivery; membranes; photolysis; prodrugs