Golgi-targeted NIR fluorescent probe with large stokes shift for real-time monitoring of nitric oxide in depression model.

Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases.

A novel lysosomal targeted near-infrared probe for ratio detection of carbon monoxide in cells and in vivo.

Carbon monoxide (CO) as an endogenous gas signaling molecule possesses important physiological functions and is of great significance in the treatment of various diseases. Real-time tracking of CO in living organisms has become a research hotspot in recent years. This article presents a lysosomal targeted near-infrared ratio fluorescence probe (TBM-CO) for selective detection of CO based on the dicyanoisophorone skeleton and morpholine fragment. The probe TBM-CO with weak ICT effect can be transformed to precursor TBM-NH2 with strong ICT effect by the traditional Tsuji-Trost reaction procession in the presence of Pd2+ ions. The mechanism was proved by DFT calculation or the MS and HPLC results respectively. In the near-infrared region an obvious ratio fluorescence intensity change (F686 / F616) is observed in vitro spectral experiments. The concentration titration experiments indicate that there is a good liner relationship between the ratio fluorescence intensity and the concentration in the range of 0 to 50 µM (R2 = 0.996) and the detection limit is calculated as 0.38 µM. The cell fluorescence imaging and co-localization experiments further demonstrate that TBM-CO is able to detect the exogenous and endogenous CO in lysosomal subcellular organelle. Finally, it was used to detect the changes of CO concentration in living mice successfully. In short, a probe with three advantages of near-infrared emission, ratiometric fluorescence and organelle targeting was reported and used to detect CO successfully in cells and in living mice.

TPE-based fluorescent probe for dual channel imaging of pH/viscosity and selective visualization of cancer cells and tissues.

The development of efficient fluorescence-based detection tools with high contrast and accuracy in cancer diagnosis has recently attracted extensive attention. Changes in the microenvironments between cancer and normal cells provide new biomarkers for precise and comprehensive cancer diagnosis. Herein, a dual-organelle-targeted probe with multiple-parameter response is developed to realize cancer detection. We designed a tetraphenylethylene (TPE)-based fluorescent probe TPE-PH-KD connected with quinolinium group for simultaneous detection of viscosity and pH. Due to the restriction on the double bond's rotation, the probe respond to viscosity changes in the green channel with extreme sensitivity. Interestingly, the probe exhibited strong emission of red channel in acidic environment, and the rearrangement of ortho-OH group occurred in the basic form with weak fluorescence when pH increased. Additionally, cell colocalization studies revealed that the probe was located in the mitochondria and lysosome of cancer cells. Following treatment with carbonyl cyanide m-chloro phenylhydrazone (CCCP), chloroquine, and nystatin, the pH or viscosity changes in the dual channels are also monitored in real-time. Furthermore, the probe TPE-PH-KD could effectively discriminate cancer from normal cells and organs with high-contrast fluorescence imaging, which sparked more research on an efficient tool for highly selectively visualizing tumors at the organ level.