title: Cell-mediated assembly of phototherapeutics.
abstract: Light-activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light-sensitive prodrugs are typically converted to their active forms using short-wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte-mediated assembly of long-wavelength-sensitive phototherapeutics. The activating wavelength of the constructs is readily preassigned by using fluorophores with the desired excitation wavelength λ(ex). Drug release from the erythrocyte carrier was confirmed by standard analytical tools and by the expected biological consequences of the liberated drugs in cell culture: methotrexate, binding to intracellular dihydrofolate reductase; colchicine, inhibition of microtubule polymerization; dexamethasone, induced nuclear migration of the glucocorticoid receptor.
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: Weston J
authors.initials: WJ
authors.lastname: Smith
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Oien
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hughes
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marvin
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Rodgers
authors.forename: Junghyun
authors.initials: J
authors.lastname: Lee
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry / Q000633:toxicity; D003907:Dexamethasone / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D004912:Erythrocytes / Q000737:chemistry*; D019793:Fluorescein / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008727:Methotrexate / Q000737:chemistry / Q000633:toxicity; D011355:Prodrugs / Q000737:chemistry* / Q000633:toxicity; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014805:Vitamin B 12 / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011355:Prodrugs; D011965:Receptors, Glucocorticoid; D012235:Rhodamines; C005358:tetramethylrhodamine; D003907:Dexamethasone; D013762:Tetrahydrofolate Dehydrogenase; D014805:Vitamin B 12; D003078:Colchicine; D019793:Fluorescein; D008727:Methotrexate
keywords: cobalamins; drug delivery; photochemistry; prodrugs