期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 34, 页码 18860-18866出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202105905
关键词
acoustogenic probe; Alzheimer's disease; analyte sensing; hydrogen peroxide; photoacoustic imaging
资金
- National Institutes of Health [R35GM133581, R01GM114588, R15GM142103-01]
- XSEDE grant [TG-CHE200009]
- Chemistry-Biology Interface Training Grant [T32-GM136629]
- RobertC. and CarolynJ. Springborn Graduate Fellowship
- Alfred P. Sloan Foundation
- RoyJ. Carver Charitable Trust (Muscatine, Iowa) [15-4521]
- National Science Foundation, Division of Biological Infrastructure [DBI-0100085]
The study introduced a new dye scaffold, PA-HD, optimized for PA probe development with enhanced sensitivity and red-shift properties. Computational modeling was used to elucidate the origin of these enhanced properties.
Most photoacoustic (PA) imaging agents are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for PA applications. Herein, we introduce PA-HD, a new dye scaffold optimized for PA probe development that features a 4.8-fold increase in sensitivity and a red-shift of the lambda(abs) from 690 nm to 745 nm to enable ratiometric imaging. Computational modeling was used to elucidate the origin of these enhanced properties. To demonstrate the generalizability of our remodeling efforts, we developed three probes for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and H2O2 (PA-HD-H2O2). We generated two cancer models to evaluate PA-HD-Gal and PA-HD-NTR. We employed a murine model of Alzheimer's disease to test PA-HD-H2O2. There, we observed a PA signal increase at 735 nm of 1.79 +/- 0.20-fold relative to background, indicating the presence of oxidative stress. These results were confirmed via ratiometric calibration, which was not possible using the parent HD platform.
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