Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation

Abstract

Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.

Dual Enzyme-Locked Activation Reporter for Accurate Liver Cancer Surveillance

“…However, the monolayer of cells does not represent the complexity of the real tumor. Therefore, we further investigated whether it was still able to distinguish cancer cells from normal cells in the 3D cell sphere model of multilayer cell culture. , As shown in Figure A,B, the red fluorescence signal of Si-NTR-LAP in HL-7702 cells was very weak, while the intensity of red fluorescence in HepG2 cells was very strong, suggesting that the probe was more inclined to enter cancer cells. And there was no obvious yellow signal overlapping green and red signals in the whole mixed culture 3D cell spheres, which indicated that the probe was still able to distinguish cancer cells from normal cells well even at the level of multilayer mixed culture cells.…”

Si–rhodamine derivative with a large stokes shift for ELISA-based detection of SARS-CoV-2

“…In recent years, xanthene dyes have emerged as exceptionally useful probes for biological imaging. 16–19 Replacing the oxygen atom in xanthene with an Si moiety results in a bathochromic shift of ∼100 nm, which can prevent self-quenching due the excitation light and benefit the testing process. Unfortunately, no fluorescent dye with a large Stokes shift (>150 nm) has been adopted in the labelling of IgG antibodies.…”