Optical imaging is a safe, cost-effective, rapid imaging modality, which can be multiplexed or engineered to
have a turn-on response. Despite these advantages, optical imaging is not widely employed in the clinic due to
the poor penetration of light through tissue and high background signal from endogenous chromophores. The
shortwave infrared (SWIR) region of the electromagnetic spectrum has emerged as an optimal region for
optical imaging due to the decreased scattering of light by tissue and minimal autofluorescence of endogenous
biomolecules in this region. The potential of the SWIR has been showcased using carbon nanotubes and
quantum dots as contrast agents; however, toxicity concerns regarding these materials prevent their clinical
translation. What is necessary are bright, non-toxic shortwave infrared fluorophores.
Recently, we have reported a bright polymethine fluorophore, deemed Flav7, which absorbs and emits
shortwave infrared light. We will take this exciting first generation compound and transform Flav7 into a water-
soluble contrast agent that can be appended to targeting agents and biomolecules of interest. We will improve
nanomaterial formulations of Flav7 by synthesizing fluorous-soluble variants. Simultaneously, we will modify
the chromophore structure to enhance the photophysical properties and access fluorophores that can be
employed simultaneously for multiplexed SWIR imaging. Lastly, we will develop SWIR quenchers, which will
be linked to the fluorophores using protease-cleavable peptide sequences to access SWIR responsive probes.
Responsive probes offer enhanced signal-to-noise ratios and eliminate the need to wait for fluorophores to
clear. Visible and near-infrared versions of similar responsive probes are currently in clinical trials for image-
guided surgery. Collectively, our fluorophore development work will provide the foundation for intraoperative
imaging, fluorescent endoscope-based diagnostics, and optical mammography.