Single- and multi-modal molecular probes with second near-infrared activatable optical signals for disease diagnosis...

Optical imaging in the second near-infrared window (NIR-II, 1000-1700 nm) enables real-time visualization of deep tissues with a higher signal-to-noise ratio than that enabled by visible and first NIR (NIR-I, 700-1000 nm) imaging owing to reduced tissue scattering and lower tissue autofluorescence. Its imaging capability can be further enhanced by integrating other imaging modalities, providing complementary biological information in living subjects. In parallel, activatable molecular probes have been designed to change signals only in the presence of biomarkers of interest, offering higher detection sensitivity and specificity than traditional "always-on" probes. These probes can also act as delivery vehicles for therapeutics, providing opportunities for precise imaging-guided therapy. This review highlights the recent advances in the development of single- and multi-modal molecular probes with NIR-II activatable optical signals for disease detection and theranostics. We begin by introducing the probe's design strategies, focusing on molecular mechanisms that enable activatable NIR-II optical signal output and biomarker specificity. Next, strategies to optimize the probe's performance in terms of improving its optical properties and overcoming biological barriers are discussed. Subsequently, the diagnostic and theranostic applications of these probes are detailed with representative examples across various in vivo disease models and in vitro tissue biopsy. Finally, we discuss the challenges and future perspectives for improving their diagnostic accuracy and precision theranostic capabilities in this emerging field.