Scott Hilderbrand, PhD
Instructor (Chemistry), Harvard Medical School Phone: 617-643-5679 Email: scott_hilderbrand@hms.harvard.edu Our research group is focused on the development of emerging fluorochrome and nanoparticle technologies for molecular imaging applications. To image effectively in vivo, dyes with absorption and fluorescence emission maxima in the NIR (650-950 nm) are necessary. Active research projects are centered on the synthesis of fluorochromes with enhanced optical characteristics for labeling, use in enzyme activated probes, and design of environment-responsive fluorogenic probes. Additional projects are focused on the construction of improved fluorescence and/or multimodal nanoparticle-based imaging platforms. Currently, we are investigating synthesis of modified NIR dyes that are optimized for labeling nano-scaffolds such as cross-linked iron oxide (CLIO) particles, bacteriophage, and poly lactic-co-glyclolic acid (PLGA) nanoparticles. Nanoparticles based on these new dyes will offer improved signal for a multitude of targeted and fluorogenic imaging applications. Another area of interest is the development NIR fluorochromes, which display altered optical properties upon changes in their local microenvironments. Projects include the design of dyes that respond to alterations of local ion concentrations, dielectric constant shifts, and oxidizing environments. One emerging application of these environment-responsive fluorochomes is in atherosclerosis imaging. Myleoperoxidase, an enzyme that is highly upregulated in vulnerable atherosclerotic plaques, produces hypochlorite, a strong oxidant under physiological conditions. A new naphthofluorescein based probe currently under development in our laboratory is activated selectively by hypochlorite. With this hypochlorite-responsive fluorochrome, we hope to ultimately image and identify vulnerable plaques. Publications Fast and Sensitive Pretargeted Labeling of Cancer Cells through a Tetrazine/trans-Cyclooctene Cycloaddition.
Angew Chem Int Edit. 2009;48(38):7013-6 - PMID: 19697389 - PMCID: PMC2790075
Oxazine Conjugated Nanoparticle Detects in Vivo Hypochlorous Acid and Peroxynitrite Generation.
J Am Chem Soc. 2009;131(43):15739-44 - PMID: 19817443 - PMCID: PMC2773134
Near-infrared fluorescence: application to in vivo molecular imaging.
Curr Opin Chem Bio. 2009;14:1-9 - PMID: 19879798
Upconverting luminescent nanomaterials: application to in vivo bioimaging.
Chem Commun. 2009;28:4188-90 - PMID: 19585016 - PMCID: PMC2748243
A DNA-binding Gd chelate for the detection of cell death by MRI.
Chem Commun. 2009;(29):4444-6 - PMID: 19597620 - PMCID: PMC2754278
Transillumination fluorescence imaging in mice using biocompatible upconverting nanoparticles
Opt Lett. 2009;34(17):2566-8 - PMID: 19724491 - PMCID: PMC2749971
Divergent Oriented Synthesis For the Design of Reagents for Protein Conjugation.
J Comb Chem. 2009;12(1):57-64 - PMID: 19928910
Labels and probes for live cell imaging: overview and selection guide.
Methods Mol Biol. 2009;591:17-45 - PMID: 19957122
Near Infrared Fluorescence-Based Bacteriophage Particles for Ratiometric pH Imaging.
Bioconjugate Chem. 2008;19(8):1635-9 - PMID: 18666791 - PMCID: PMC2705288
Tetrazine-Based Cycloadditions: Application to Pretargeted Live Cell Imaging.
Bioconjugate Chem. 2008;19(12):2297-2299 - PMID: 19053305 - PMCID: PMC2677645
Monofunctional Carbocyanine Dyes for Bio- and Bioorthogonal Conjugation.
Bioconjugate Chem. 2008;19(12): :2487-2491 - PMID: 19053316 - PMCID: PMC2656649
Design and demonstration of a small-animal up-conversion imager.
Optics Express. 2008;16 (26):21731-7 - PMID: 19104605 - PMCID: PMC2717740
A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages.
Chem Biol. 2007;14:1221-31 - PMID: 18022561 - PMCID: PMC2785040
Optimized pH-responsive cyanine fluorochromes for detection of acidic environments
Chem Commun. 2007;(26):2747-9 - PMID: 17594041
Sugar sensing based on induced pH changes
Chem Commun. 2007;(22):2299-2301 - PMID: 17534523
A Highly Selective Fluorescent Probe for Thiol Bioimaging.
Org Lett. 2007;10 :37-40 - PMID: 18062694
One-Pot Synthesis of New Symmetric and Asymmetric Xanthene Dyes.
Tetrahedron Lett. 2007;48(25):4383-4385 - PMID: 19834587 - PMCID: PMC2761723
Enzyme-targeted fluorescent imaging probes on a multiple antigenic peptide core
J Med Chem. 2006;49(15):4715-20 - PMID: 16854078
Monofunctional near-infrared fluorochromes for imaging applications
Bioconjugate Chem. 2005;16(5):1275-81 - PMID: 16173808
Cobalt chemistry with mixed aminotroponiminate salicylaldiminate ligands: synthesis, characterization, and nitric oxide reactivity.
Inorg Chem. 2005;43:4674-82 - PMID: 15257596
Dirhodium tetracarboxylate scaffolds as reversible fluorescence-based nitric oxide sensors.
J Am Chem Soc. 2004;126:4972-8 - PMID: 15080703
Synthesis and characterization of zinc sensors based on a monosubstituted fluorescein platform.
Inorg Chem. 2004;43:2624-35 - PMID: 15074981
Nitric oxide reactivity of fluorophore coordinated carboxylate-bridged diiron(II) and dicobalt(II) complexes.
Inorg Chem. 2004;43:5294-301 - PMID: 15310207
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Scott Hilderbrand, PhD