title: Double click: dual functionalized polymeric micelles with antibodies and peptides.
abstract: Polymeric nanoparticle micelles provide a possible platform for theranostic delivery, combining the role of therapeutics and diagnostics in one vehicle. To explore dual-functional micelles, the amphiphilic copolymer of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol)-X (P(LA-co-TMCC)-g-PEG-X) was self-assembled to form micelles, with X representing either azide or furan. Micelles of P(LA-co-TMCC)-g-PEG-azide and P(LA-co-TMCC)-g-PEG-furan terminal functional groups were used to conjugate dibenzylcyclooctyne and maleimide-modified probes, respectively, taking advantage of orthogonal coupling chemistry. To verify the utility of the dual-functional micelles, trastuzumab-maleimide antibodies and FLAG-dibenzylcyclooctyne peptides were covalently bound by sequential click chemistry reactions. SKOV-3luc cells that were treated with the dual-functionalized micelles showed colocalization of the antibodies and peptides by confocal imaging, demonstrating the promise of this approach.
authors.affiliation: Department of Chemical Engineering & Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
authors.forename: Dianna P Y
authors.initials: DP
authors.lastname: Chan
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Owen
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000480:Alkynes / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis / Q000737:chemistry*; D001386:Azides / Q000737:chemistry; D002232:Carbocyanines / Q000032:analysis; D002254:Carbonates / Q000737:chemistry; D045744:Cell Line, Tumor; D057930:Click Chemistry; D005663:Furans / Q000737:chemistry; D006801:Humans; D006834:Hydrazines / Q000032:analysis; D008301:Maleimides / Q000737:chemistry; D008823:Micelles; D009842:Oligopeptides; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000068878:Trastuzumab
chemical_list: C417561:Alexa 488 hydrazide; C569686:Alexa Fluor 647; D000480:Alkynes; D061067:Antibodies, Monoclonal, Humanized; D001386:Azides; D002232:Carbocyanines; D002254:Carbonates; D005663:Furans; D006834:Hydrazines; D008301:Maleimides; D008823:Micelles; D009842:Oligopeptides; D010455:Peptides; D011091:Polyesters; C043592:maleimide; D011092:Polyethylene Glycols; C033616:poly(lactide); C042001:1-octyne; C085706:FLAG peptide; D000068878:Trastuzumab; C039281:furan