Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Department of Chemistry and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, I, L, 61801, USA.
Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18860-18866. doi: 10.1002/anie.202105905. Epub 2021 Jul 1.
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 λ 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 β-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and H O (PA-HD-H O ). 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-H O . 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.
大多数光声 (PA) 成像剂都是基于对现有荧光染料平台的再利用，这些平台在 PA 应用中表现出非最佳的性能。在此，我们引入了 PA-HD，这是一种新的染料支架，专为 PA 探针开发而优化，其灵敏度提高了 4.8 倍，λ从 690nm 红移至 745nm，实现了比率成像。计算建模用于阐明这些增强性能的起源。为了证明我们的改造工作的通用性，我们开发了三种用于β-半乳糖苷酶活性 (PA-HD-Gal)、硝基还原酶活性 (PA-HD-NTR) 和 H O 的探针 (PA-HD-H O )。我们生成了两种癌症模型来评估 PA-HD-Gal 和 PA-HD-NTR。我们采用阿尔茨海默病的小鼠模型来测试 PA-HD-H O 。在那里，我们观察到相对于背景的 735nm 处的 PA 信号增加了 1.79±0.20 倍，表明存在氧化应激。这些结果通过比率校准得到了证实，而使用母体 HD 平台则不可能进行比率校准。
