Luo Jinlan, Song Changyong, Chen Yunling, Liu Keyin
State Key Laboratory of Biobased Material and Green Papermaking, Key Laboratory of Pulp & Paper Science and Technology of Shandong Province/Ministry of Education, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China.
Chem Biomed Imaging. 2024 Jan 3;2(6):422-431. doi: 10.1021/cbmi.3c00110. eCollection 2024 Jun 24.
Blood viscosity changes and blood clots are high-impact diseases, but the pathogenic mechanisms and detection methods are still limited. Due to the complexity of the cellular microenvironment, viscosity is a key factor in regulating the behavior of mitochondria and lysosomes in cells. Conventional fluorescence probes are highly restrictive for complex viscosity detection in live animals. Therefore, we developed two near-infrared fluorescence probes, and , with dual responses to the pH and viscosity. Notably, has two maximum fluorescence emissions at 680 and 750 nm, when excitation by 580 and 700 nm, respectively. exhibited both a pH and viscosity switchable fluorescence response. The two emission peaks exhibited a reverse change trend: the fluorescence at 680 nm decreased by 90%, and the fluorescence at 750 nm increased by about 5-fold with pH from 2 to 10. Meanwhile, both emission peaks show remarkable fluorescence enhancement toward viscosity change, with 185 and 32 times enhancement, respectively. The sensing mechanism and spectral changes are confirmed by DFT calculations. was further used for viscosity imaging in live cells, zebrafish, and live animals. Most importantly, is able to successfully track changes in blood clots in live mice and organs, thus enabling the study of blood clots in cerebral strokes and the underlying pathological mechanisms.
血液粘度变化和血栓形成是高影响性疾病，但其致病机制和检测方法仍然有限。由于细胞微环境的复杂性，粘度是调节细胞中线粒体和溶酶体行为的关键因素。传统荧光探针对活体动物中复杂粘度检测的限制很大。因此，我们开发了两种对pH值和粘度具有双重响应的近红外荧光探针，即 和 。值得注意的是， 分别在580和700nm激发时，在680和750nm处有两个最大荧光发射峰。 表现出pH值和粘度可切换的荧光响应。两个发射峰呈现相反的变化趋势：随着pH值从2变为10，680nm处的荧光降低了90%，750nm处的荧光增加了约5倍。同时，两个发射峰对粘度变化均表现出显著的荧光增强，分别增强了185倍和32倍。通过密度泛函理论（DFT）计算证实了传感机制和光谱变化。 进一步用于活细胞、斑马鱼和活体动物的粘度成像。最重要的是， 能够成功跟踪活体小鼠和器官中血栓的变化，从而有助于研究中风中的血栓及其潜在病理机制。
