The scarcity of high-performance fluorophores remains a formidable bottleneck in the rapidly advancing field of NIR-II imaging, as existing candidates suffer from low light absorptivity, poor emission efficiency, and cumbersome synthesis. Herein, we propose a straightforward 2-step cyclization strategy to construct an innovative highly bright NIR-II dye family designated as BM-engineering from readily available materials. BM dyes featured a fully rigid and coplanar skeleton, exhibiting superior molar extinction coefficient (εDCM = 1.9-3.7 × 105 M-1 cm-1), high fluorescence quantum yields (ΦF = 10.4-18.0% in DCM), and remarkable photochemical robustness. Notably, BM3 redefines the optical landscape with its exceptional NIR-II optical performance (ε = 3.7 × 105 M-1 cm-1, ΦF = 18.4%), solidifying its status as the brightest NIR-II fluorophore reported to date. Leveraging this advantage, BM3 achieves high-resolution bioimaging at ultralow doses, not only illuminating cerebral vasculature (3 nmol) and lymphatic vessels (75 pmol), but also accurately detecting subtle cerebral capillary damage in ischemia-reperfusion models. More strikingly, BM3 provides the first precise real-time tracking of inflamed lymphatic system triggered by both chemical and bacterial stimuli, unveiling distinct pathophysiological patterns that were previously elusive. Beyond experimental validation, computational analysis further deciphers the intricate relationship between molecular architecture and optical performance, offering new insight into the rational design of next-generation NIR-II fluorophores. This study not only pioneers a streamlined synthesis strategy toward ultrabright NIR-II fluorophores but also expands the frontiers of bioimaging precision and disease diagnostics, unlocking immense potential for biomedical innovations and clinical applications.
Bian et al. (2025) studied this question.