Design strategies and biomedical applications of organic NIR-IIb fluorophores

The introduction of fluorescence imaging (FLI) in near-infrared II sub-channels (NIR-IIb, 1500–1700 nm) has revolutionized the ability to explore complex patho-physiological settings in vivo. Despite the transformative potentials, the development of organic NIR IIb dyes encounters considerable difficulties, and only a limited number of such fluorophores have been developed so far. This review systematically introduces design strategies of organic NIR-IIb fluorophores classified by molecular scaffolds, mainly including cyanine dyes and D–A–D small molecule dyes. The design strategies of cyanine dyes involve repurposing of the existing NIR dyes, conjugate reinforcement and regulation of the aggregation state. For D–A–D small molecule dyes, strategies mainly incorporate the extension of the conjugate skeleton, introduction of shielding units, and acceptor/donor engineering. We further describe recent biomedical applications including biomedical imaging and imaging-guided therapy, and conclude by clarifying the current challenges and prospects of NIR-IIb FLI.