Abstract
Nanoparticles have emerged as key materials for biomedical applications because of their unique and tunable physical properties, multivalent targeting capability, and high cargo capacity1,2. Motivated by these properties and by current clinical needs, numerous diagnostic3,4,5,6,7,8,9,10 and therapeutic11,12,13 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.
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Acknowledgements
The authors gratefully acknowledge N. Sergeyev for synthesizing CLIO and C. Wang for assistance with MALDI-TOF measurements. We especially thank G. Thurber, M. Pittet, F. Swirski and M. Nahrendorf for their many helpful suggestions. We also thank Y. Fisher-Jeffes for reviewing the manuscript. This work was funded in part by NCI grant P50CA86355 and RO1 EB004626.
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J.B.H. designed and performed the experiments, analysed the data and wrote the manuscript. N.K.D. and S.A.H. developed and synthesized the bioorthogonal chemistries. H.L. performed the magnetic resonance measurements. R.W. provided overall guidance, designed experiments, reviewed the data and wrote the manuscript. All authors discussed the results and commented on the manuscript.
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Haun, J., Devaraj, N., Hilderbrand, S. et al. Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection. Nature Nanotech 5, 660–665 (2010). https://doi.org/10.1038/nnano.2010.148
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DOI: https://doi.org/10.1038/nnano.2010.148
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