Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
Institute for Experimental Molecular Imaging University Clinic, RWTH Aachen University, Forckenbeckstra. 55, 52074 Aachen, Germany.
ACS Sens. 2021 Dec 24;6(12):4379-4388. doi: 10.1021/acssensors.1c01674. Epub 2021 Dec 13.
Short-lived reactive intermediates such as reactive oxygen species (ROS) regulate many physiological processes, but overproduction can also lead to severe tissue dysfunction. Thus, there is a high demand for noninvasive detection of reactive molecules, which, however, is challenging. Herein, we report photoacoustic detection of ROS using conjugated BODIPY probes (ROS-BODIPYs). The ROS reaction with conjugated BODIPYs induced a redshift in absorption by ∼100 nm into the near infrared (from ∼700 to ∼800 nm), quenched fluorescence, and generated strong photoacoustic (PA) signals. Thus, the ROS-activated and ROS-nonactivated states of ROS-BODIPYs can be detected in vivo by PA and fluorescence imaging. Interestingly, ROS activation is reversible, in the presence of excess reducing agents, e.g., citric acid, converted back to its original state, suggesting that ROS-BODIPYs can be useful for the detection of over production of ROS but not physiological amounts. This makes the imaging independent of accumulation of the activated probe with the physiological ROS amounts and thus strongly improves applicability and highlights the translational potential of ROS-BODIPYs for detecting overexpression of ROS in vivo by optical and photoacoustic imaging methods.
短寿命的活性中间体，如活性氧物种 (ROS)，调节许多生理过程，但过量产生也会导致严重的组织功能障碍。因此，人们对非侵入性检测活性分子有很高的需求，但这是具有挑战性的。在此，我们报告了使用共轭 BODIPY 探针 (ROS-BODIPYs) 进行 ROS 的光声检测。ROS 与共轭 BODIPY 的反应导致吸收向近红外（从约 700nm 到约 800nm）红移约 100nm，荧光猝灭，并产生强的光声（PA）信号。因此，ROS-BODIPY 的 ROS 激活和非激活状态可以通过 PA 和荧光成像在体内检测到。有趣的是，ROS 的激活是可逆的，在过量的还原剂（如柠檬酸）存在下，它会转回到原来的状态，这表明 ROS-BODIPY 可用于检测 ROS 的过量产生，但不能用于检测生理量的 ROS。这使得成像与生理 ROS 量的激活探针的积累无关，从而大大提高了适用性，并突出了 ROS-BODIPY 用于通过光学和光声成像方法检测体内 ROS 过表达的转化潜力。
