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A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing

preprint
submitted on 28.04.2021, 03:44 and posted on 29.04.2021, 04:58 by Sarah Garder, Catharine Brady, Cameron Keeton, Anuj K Yadav, Sharath C Mallojjala, Melissa Lucero, ShengZhang Su, Zhengxin Yu, Jennifer S. Hirschi, Liviu M. Mirica, Jefferson Chan

In the context of deep-tissue disease biomarker detection and analyte sensing of biologically relevant species, the impact of photoacoustic imaging has been profound. However, most photoacoustic imaging agents to date are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for photoacoustic applications (e.g., high fluorescence quantum yield). Herein, we introduce two effective modifications to the hemicyanine dye to afford PA-HD, a new dye scaffold optimized for photoacoustic probe development. We observed a significant increase in the photoacoustic output, representing an increase in sensitivity of 4.8-fold and a red-shift of the λabs from 690 nm to 745 nm to enable ratiometric imaging. Moreover, to demonstrate the generalizability and utility of our remodeling efforts, we developed three probes using common analyte-responsive triggers for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and hydrogen peroxide (PA-HD-H2O2). The performance of each probe (responsiveness, selectivity) was evaluated in vitro and in cellulo. To showcase the enhance properties afforded by PA-HD for in vivo photoacoustic imaging, we employed an Alzheimer’s disease model to detect H2O2. In particular, the photoacoustic signal at 735 nm in the brains of 5xFAD mice (a murine model of Alzheimer’s disease) increased by 1.72 ± 0.20-fold relative to background indicating the presence of oxidative stress, whereas the change in wildtype mice was negligible (1.02 ± 0.14). These results were confirmed via ratiometric calibration which was not possible using the parent HD platform.

Funding

Chemical Tools to Study the Role of Biological Aldehydes

National Institute of General Medical Sciences

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Novel Bifunctional Chemical Agents as Theranostic Tools for Amyloid Diseases

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

jeffchan@illinois.edu

Institution

University of Illinois at Urbana-Champaign

Country

United States

ORCID For Submitting Author

0000-0003-4139-4379

Declaration of Conflict of Interest

No conflict of interest

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