title: Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection.
abstract: Nanoparticles have emerged as key materials for biomedical applications because of their unique and tunable physical properties, multivalent targeting capability, and high cargo capacity. Motivated by these properties and by current clinical needs, numerous diagnostic and therapeutic nanomaterials have recently emerged. Here we describe a novel nanoparticle targeting platform that uses a rapid, catalyst-free cycloaddition as the coupling mechanism. Antibodies against biomarkers of interest were modified with trans-cyclooctene and used as scaffolds to couple tetrazine-modified nanoparticles onto live cells. We show that the technique is fast, chemoselective, adaptable to metal nanomaterials, and scalable for biomedical use. This method also supports amplification of biomarker signals, making it superior to alternative targeting techniques including avidin/biotin.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, Massachusetts 02114, USA.
authors.forename: Jered B
authors.initials: JB
authors.lastname: Haun
authors.forename: Neal K
authors.initials: NK
authors.lastname: Devaraj
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hilderbrand
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015374:Biosensing Techniques / Q000191:economics / Q000379:methods*; D045744:Cell Line, Tumor; D034242:Cyclooctanes / Q000737:chemistry; D005453:Fluorescence; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008280:Magnetics; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis
chemical_list: D000906:Antibodies; D015415:Biomarkers; D034242:Cyclooctanes; D006573:Heterocyclic Compounds, 1-Ring