Design strategies and applications of smart optical probes in the second near-infrared window

Over the last decade, a series of synergistic advances in the synthesis chemistries and imaging instruments have largely boosted a significant revolution, in which large-scale biomedical applications are now benefiting from optical bioimaging in the second near-infrared window (NIR-II, 1000–1700 nm). The large tissue penetration and limited autofluorescence associated with long-wavelength imaging improve translational potential of NIR-II imaging over common visible-light (400–650 nm) and NIR-I (750–900 nm) imaging, with ongoing profound effects on the studies of precision medicine. Unfortunately, the majority of NIR-II probes are designed as “always-on” luminescent imaging contrasts, continuously generating unspecific signals regardless of whether they reach pathological locations. Thus, in vivo imaging by traditional NIR-II probes usually suffers from weak detect precision due to high background noise. In this context, the advances of optical imaging now enter into an era of precise control of NIR-II photophysical kinetics. Developing NIR-II optical probes that can efficiently activate their luminescent signal in response to biological targets of interest and substantially suppress the background interferences have become a highly prospective research frontier. In this review, the merits and demerits of optical imaging probes from visible-light, NIR-I to NIR-II windows are carefully discussed along with the lens of stimuli-responsive photophysical kinetics. We then highlight the latest development in engineering methods for designing smart NIR-II optical probes. Finally, to appreciate such advances, challenges and prospect in rapidly growing study of smart NIR-II probes are addressed in this review.