Scott Hilderbrand


PI Bio

Hilderbrand, Scott, PhD

Phone: 617-643-5679


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.

Selected Publications (from total of 39)

Desai RM, Koshy ST, Hilderbrand SA, Mooney DJ, Joshi NS
Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry.
Biomaterials . 2015;50:30-7 - PMID: 25736493 - DOI: 10.1016/j.biomaterials.2015.01.048
Wollack JW, Monson BJ, Dozier JK, Dalluge JJ, Poss K, Hilderbrand SA, Distefano MD
Site-Specific Labeling of Proteins and Peptides with Trans-cyclooctene Containing Handles Capable of Tetrazine Ligation.
Chem Biol Drug Des. 2014;84(2):140-7 - PMID: 24899362 - PMCID: PMC4107141 - DOI: 10.1111/cbdd.12303
Tassa C, Liong M, Hilderbrand S, Sandler JE, Reiner T, Keliher EJ, Weissleder R, Shaw SY
Microfluidic On-chip Capture-cycloaddition Reaction to Reversibly Immobilize Small Molecules or Multi-component Structures for Biosensor Applications.
J Vis Exp. 2013;(79):e50772 - PMID: 24084440 - PMCID: PMC3924759 - DOI: 10.3791/50772
Carlson JC, Meimetis LG, Hilderbrand SA, Weissleder R
BODIPY-Tetrazine Derivatives as Superbright Bioorthogonal Turn-on Probes.
Angew Chem Int Ed Engl. 2013;52(27):6917-6920 - PMID: 23712730 - PMCID: PMC3875324 - DOI: 10.1002/anie.201301100
Shan G, Weissleder R, Hilderbrand SA
Upconverting Organic Dye Doped Core-Shell Nano-Composites for Dual-Modality NIR Imaging and Photo-Thermal Therapy.
Theranostics. 2013;3(4):267-74 - PMID: 23606913 - PMCID: PMC3630527 - DOI: 10.7150/thno.5226
Tassa C, Liong M, Hilderbrand S, Sandler JE, Reiner T, Keliher EJ, Weissleder R, Shaw SY
On-chip bioorthogonal chemistry enables immobilization of in situ modified nanoparticles and small molecules for label-free monitoring of protein binding and reaction kinetics.
Lab Chip. 2012;12(17):3103-10 - PMID: 22760641 - PMCID: PMC3411869 - DOI: 10.1039/c2lc40337d
Hendricks JA, Keliher EJ, Wan D, Hilderbrand SA, Weissleder R, Mazitschek R
Synthesis of [(18) F]BODIPY: Bifunctional Reporter for Hybrid Optical/Positron Emission Tomography Imaging.
Angew Chem Int Ed Engl. 2012;51(19):4603-6 - PMID: 22473535 - PMCID: PMC3343182 - DOI: 10.1002/anie.201107957
Karver MR, Weissleder R, Hilderbrand SA
Bioorthogonal Reaction Pairs Enable Simultaneous, Selective, Multi-Target Imaging.
Angew Chem Int Ed Engl. 2011;51(4):920-2 - PMID: 22162316 - PMCID: PMC3304098 - DOI: 10.1002/anie.201104389
Karver M, Weissleder R, Hilderbrand SA
Synthesis and Evaluation of a Series of 1,2,4,5-Tetrazines for Bioorthogonal Conjugation.
Bioconjug Chem. 2011;22(11):2263-2270 - PMID: 21950520 - PMCID: PMC3254257 - DOI: 10.1021/bc200295y
Yoon TJ*, Lee H*, Shao H, Hilderbrand SA, Weissleder R
Multicore Assemblies Potentiate Magnetic Properties of Biomagnetic Nanoparticles.
Adv Mater. 2011;23(41):4793-7 - PMID: 21953810 - PMCID: PMC3224986 - DOI: 10.1002/adma.201102948
Zeglis BM, Mohindra P, Weissmann GI, Divilov V, Hilderbrand SA, Weissleder R, Lewis JS
A Modular Strategy for the Construction of Radiometallated Antibodies for Positron Emission Tomography Based on Inverse Electron Demand Diels-Alder Click Chemistry.
Bioconjug Chem. 2011;22(10):2048-59 - PMID: 21877749 - PMCID: PMC3197258 - DOI: 10.1021/bc200288d
Shao F, Yuan H, Josephson L, Weissleder R, Hilderbrand SA
Facile Synthesis of Monofunctional Pentamethine Carbocyanine Fluorophores.
Dyes Pigm. 2011;90(2):119-122 - PMID: 21475610 - PMCID: PMC3070263 - DOI: 10.1016/j.dyepig.2010.12.008