Dianna P Y Chan, Shawn C Owen, Molly S Shoichet
Department of Chemical Engineering & Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
Bioconjugate chemistry 2013 Jan 16Polymeric 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.
Dianna P Y Chan, Shawn C Owen, Molly S Shoichet. Double click: dual functionalized polymeric micelles with antibodies and peptides. Bioconjugate chemistry. 2013 Jan 16;24(1):105-13
PMID: 23289801
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