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Fluorescence bioimaging through the second near-infrared window (NIR-II, 1000-1700 nm) has attracted much attention due to its deep penetration and high contrast. However, exploring new fluorescent materials, especially small molecular fluorophores with long wavelength and high brightness, is still quite challenging. By expanding π-conjugation and enhancing the intramolecular charge transfer effect, herein we report a series of new xanthene-based NIR-II dyes, named VIXs. Among these dyes, VIX-4 exhibits the best performance with fluorescence emission at 1210 nm and high brightness and has been used for dynamically imaging the blood flow of mice at 200 fps. By virtue of high spatiotemporal resolution of the dynamic imaging, we can distinguish directly the artery and vein through the blood flow direction and measure the blood flow volume by the videos. This study provides not only an effective tool for high spatial and temporal resolution bioimaging but also a new and promising conjugated skeleton for NIR-II dyes.

Inflammation widely occurs in various tissues and organs in the human body. Rapid and accurate diagnosis of inflammation is essential to avoid severe complications. This study aims to obtain a non-destructive, fast, and comprehensive tool for the detection of pathogenic sites of inflammation in vivo. A fluorescence and photoacoustic dual-mode imaging probe, Cy-ASP, was first developed to detect inflammatory biomarker LTA4H with good sensitivity and selectivity in living small animal. Furthermore, the relationship between LTA4H and NF-κB in an LPS-induced cell was investigated. This work provides a new idea for the clinical diagnosis of pneumonia and hepatitis and revealing the upstream regulatory mechanism of LTA4H in the pneumonia model.

We developed a photoacoustic and fluorescent dual-mode imaging probe, CCYS, for the detection of cysteine with high selectivity and sensitivity in a living system for the first time. By using CCYS, we found that the limited synthesis of glutathione in pulmonary fibrosis was not caused by cysteine deficiency.

Golgi oxidative stress is significantly associated with the occurrence and progression of hypertension. Notably, the concentration of hydrogen peroxide (H2O2) is directly proportional to the degree of Golgi oxidative stress. Therefore, based on a novel Golgi-targeting phenylsulfonamide group, we developed a two-photon (TP) fluorescent probe, Np-Golgi, for in situ H2O2 ratiometric imaging in living systems. The phenylsulfonamide moiety effectively assists Np-Golgi in the precise location of Golgi apparatus. In addition, the raw material of phenylsulfonamide is easily available, and chemical modification is easily implemented. By application of Np-Golgi, we explored the generation of H2O2 during Golgi oxidative stress, and also successfully revealed increases on the levels of Golgi H2O2 in the kidneys of mice with hypertension. This work provides an ideal tool to monitor Golgi oxidative stress for the first time and novel drug targets for the future treatment of hypertension.

Golgi pH homeostasis affects many different biological processes, including glycosylation. Recent studies have demonstrated that transmembrane protein 165 (TMEM165) deficiency leads to Golgi glycosylation abnormalities by disturbing Golgi pH homeostasis. However, due to the lack of specific tools to measure Golgi pH in situ, evidence for TMEM165 involvement in H+ transport in the Golgi apparatus is still absent. Herein, the photoacoustic and fluorescent dual-mode probe CPH was developed for ratiometric detection of Golgi pH. CPH was proved to accumulate in the Golgi apparatus and reversibly image Golgi pH in real-time with high sensitivity in cells. Furthermore, we found that the absence of TMEM165 influenced H+ equilibrium and caused Golgi apparatus acidification. Our work provides strong evidence that TMEM165 regulates Golgi pH homeostasis. Moreover, we believe that CPH has the potential to be a practical tool to monitor Golgi pH in various biological processes.