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

A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing*.
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DOI:
10.1002/anie.202105905
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发表时间:
2021-08-16
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
--
通讯作者:
Chan J
Chan J
中科院分区:
其他
文献类型:
--
作者:
Gardner SH;Brady CJ;Keeton C;Yadav AK;Mallojjala SC;Lucero MY;Su S;Yu Z;Hirschi JS;Mirica LM;Chan J

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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 which features 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. Computational modelling was employed to elucidate the origin of these enhanced properties. Moreover, to demonstrate the generalizability of our remodeling efforts, we developed three probes for β-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. Additionally, we employed a murine model of Alzheimer’s disease to test PA-HD-H2O2. In this latter example, 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. We have developed PA-HD, a new sulfur-substituted dye platform exhibiting enhanced properties for photoacoustic probe development. To demonstrate generalizability, we employed PA-HD to access probes for beta-galactosidase and nitroreductase activities, as well as H2O2. Each probe was tested in live cells and in vivo. For instance, the H2O2 probe was employed to visualized oxidative stress in an Alzheimer’s disease model. Institute and/or researcher Twitter usernames: @ChanLabUIUC @MiricaGroup
DOI: 10.1021/acs.accounts.8b00351
发表时间: 2018-11-20
影响因子: 18.3
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