基于活性的光声探针，用于在威尔逊病和肝转移的小鼠模型中进行无活检的铜评估。
Activity-based photoacoustic probe for biopsy-free assessment of copper in murine models of Wilson's disease and liver metastasis.
机构信息
Department of Chemistry, The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Department of Chemistry, The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
出版信息
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36). doi: 10.1073/pnas.2106943118.
The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson's disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson's disease animals from healthy control mice in each instance.
我们开发了一种高性能的光声（PA）探针，可以在深层组织中监测疾病生物标志物，有潜力替代活检等有创的医学程序。然而，此类探针必须针对体内性能进行优化，并表现出卓越的安全性。在这项研究中，我们开发了 PACu-1，这是一种用于通过光声成像进行无活检肝铜评估（BFA）的 PA 探针。PACu-1 的特点是在已针对比率检测进行优化的氮杂-BODIPY 染料平台上附加了一个 Cu（I）响应触发基团。由于其出色的性能，我们能够检测到健康野生型小鼠的基础铜水平，以及威尔逊病模型和肝转移模型中的铜升高。为了展示 PACu-1 用于 BFA 的潜力，我们进行了两项盲法研究，在每项研究中，我们都能够成功地从健康对照小鼠中识别出威尔逊病动物。
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