A General Strategy for Development of Activatable NIR‐II Fluorescent Probes for In Vivo High‐Contrast Bioimaging

Abstract

Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized.

Molecular Engineering of Novel Fluorophores for High‐Contrast Bioimaging

“…Furthermore, we utilized this molecular design strategy to fabricate a second near‐infrared (NIR‐II) dye with a large Stokes shift. [ 24 ] Compared to the fluorophores with visible and first near‐infrared (NIR‐I) emissions, the NIR‐II dyes exhibited reduced autofluorescence, deeper penetration, and decreased photon scattering, which was beneficial for deep‐tissue imaging. [ 25 ] Previous studies have reported two general strategies to develop NIR‐II fluorophores.…”

A New Lipid‐Droplets‐Targeted Fluorescence Probe with Dual‐Reactive Sites for Specific Detection of ClO− in Living Cells

“…[49][50][51] However, the observations from cell imaging in vitro by fluorescent probes often cannot totally represent an agreement to the real circumstances in vivo. [52][53][54] Encouraged by the very excellent cell imaging applications, the investigating in vivo imaging of living zebrafish embryos by using TPAs-SCH 3 -2CN are reasonably carried out. Herein, owing to the exceptionally high optical clarity in embryonic and larval stages, zebrafish is recognized as an ideal vertebrate model for biological in vivo imaging.…”

Recent Advances in Second Near-Infrared Region (NIR-II) Fluorophores and Biomedical Applications

“…To address these problems, Ren et al proposed a new idea of constructing NIR-II fluorescent probes by increasing the spatial resistance and electronic asymmetry, and developed a series of stable, high quantum yield, and solvent burst resistant elite fluorophores (NIR II-RTs). In addition, due to the introduction of the carboxylic acid functional group, the new dye NIR II-RT3/4 can generate a powerful fluorescence switching mechanism through helical cyclization, and thus the NIR II-RT dye can be designed as an activatable NIR-II fluorescent probe ( Ren et al, 2020 ).…”