“Dual‐Key‐and‐Lock” NIR‐II NSCyanines Enable High‐Contrast Activatable Phototheranostics in Extrahepatic Diseases

Abstract

Conventional cyanine dyes with a symmetric structure are "always‐on", which can easily accumulate in the liver and display high liver background fluorescence, inevitably interfering the accurate diagnosis and therapy in extrahepatic diseases. We herein report a platform of NIR‐II non‐symmetric cyanine (NSCyanine) dyes by harnessing a non‐symmetric strategy, which are extremely sensitive to pH/viscosity and can be activated via a“dual‐key‐and‐lock”strategy. These NSCyanine dyes with a low pKa (<4.0) only show weak fluorescence at lysosome pH (key1), however, the fluorescence can be completely switched on and significantly enhanced by intracellular viscosity (key2) in disease tissues, exhibiting high target‐to‐liver ratios up to 19.5/1. Notably, high‐contrast phototheranostics in extrahepatic diseases are achieved, including intestinal metastasis‐imaging, acute gastritis‐imaging, bacteria infected wound healing, and tumor ablation via targeted combined photothermal therapy and chemotherapy.

Fast-Responsive HClO-Activated Near-Infrared Fluorescent Probe for In Vivo Diagnosis of Inflammatory Bowel Disease and Ex Vivo Optical Fecal Analysis

“…To further verify this pathway, RAW 264.7 cells were pretreated with different concentrations of phloretin (a classical GLUT1 inhibitor). 48 As shown in Figure 4C and D, the NIR fluorescence dramatically decreased for the cells treated with phloretin. These results confirmed that the uptake of probe Cy-DM is mainly mediated by MRC1 and GLUT1 on the cell membrane.…”

“…Besides, there was a negative correlation between fluorescence intensity and d -mannosamine concentration (Figure B). To further verify this pathway, RAW 264.7 cells were pretreated with different concentrations of phloretin (a classical GLUT1 inhibitor) . As shown in Figure C and D, the NIR fluorescence dramatically decreased for the cells treated with phloretin.…”

Acid-promoted fluorescent probe for monitoring endogenous methylglyoxal in tumors and gastritis

“…5a). 38 30 min later, 150 μL of Cy-DNH 2 was injected into the stomachs of the mice, and fluorescence imaging was performed. The fluorescence signals of mice with gastritis were significantly higher than those of healthy mice (Fig.…”

Mechanistic analysis of viscosity-sensitive fluorescent probes for applications in diabetes detection

“…Keeping this in mind, four non-symmetrical cynanine dyes were designed by Yang Tian and his colleagues. 94 The novelty of their system relied on the dual activation nature under acidic (4–5.5) and highly viscous medium. At the lysosomal pH, dyes with p K a less than 4 exhibited a transition from non-fluorescent to weak NIR fluorescence.…”