A Versatile Aza-BODIPY-Based Activatable Probe for High-Contrast NIR-II Biosensing

Activatable molecular probes in the second near-infrared (NIR-II, 900−1700 nm) window are sought-after for in vivo optical imaging and biosensing. However, current molecular skeletons are confined to a limited range of dye systems, including cyanine, hemicyanine, and xanthene derivatives. Herein, we report a series of ortho-halogenated phenol-conjugated aza boron dipyrromethene platforms (OBDP-xOH, where X = H, F, Cl, Br, or 2Cl) that achieve bright NIR-II emission through a pH-regulated intramolecular charge transfer mechanism. The optimized scaffold, OBDP-2ClOH (pKa = 6.1), concurrently demonstrates the NIR-II emission maximum at approximately 905 nm, a large Stokes shift of 117 nm, high NIR-II brightness (εmaxΦf>1000 nm ≈ 38.46 M−1 cm−1), and excellent photochemical stability. To validate the broad applicability of this platform, we further designed three target-activatable NIR-II nanoprobes responsive to UV light, H2S, and Cu2+, respectively. Each nanoprobe exhibited a high fluorescence turn-on ratio exceeding 29-fold and limits of detection below 10.3 nM. Leveraging these probes, we achieved rapid (<30 min) dynamic imaging of labile Cu2+ in the brains of Parkinson’s disease models, as well as high-fidelity in vivo early detection of acute liver injury within 5 min, which is substantially faster than conventional clinical serum analysis that requires approximately 90 min. Collectively, these findings underscore the translational potential of the OBDP-2ClOH scaffold as a versatile and generalizable platform for the development of advanced activatable NIR-II probes.