title: Core-clickable PEG-branch-azide bivalent-bottle-brush polymers by ROMP: grafting-through and clicking-to.
abstract: The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic structures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (∼6-∼50 nm); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
authors.forename: Jeremiah A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Lu
authors.forename: Alan O
authors.initials: AO
authors.lastname: Burts
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Lim
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Koberstein
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turro
authors.forename: David A
authors.initials: DA
authors.lastname: Tirrell
authors.forename: Robert H
authors.initials: RH
authors.lastname: Grubbs
mesh_terms: D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D002850:Chromatography, Gel; D003300:Copper / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D049329:Nanostructures; D011092:Polyethylene Glycols / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D001386:Azides; D011092:Polyethylene Glycols; D003300:Copper; D004317:Doxorubicin