Ultrabright 1650 nm-Emitting Biodegradable Organic Luminophores for NIR-IIbc Fluorescence Imaging

Near-infrared IIbc (NIR-IIbc, 1500-2000 nm) fluorescence imaging permits unprecedented resolution for deep-tissue visualization, driving the high demand for organic NIR-IIbc materials due to their tunable optical properties, versatile functionalization, and excellent biocompatibility. However, nearly all existing organic probes emit peaks below 1500 nm in H2O with emission tails extending only to 1600 nm and raise biosafety concerns due to slow hepatobiliary clearance. These limitations hinder the full potential of NIR-IIbc imaging. Herein, we report a planar ambipolar unit-acceptor design to develop biodegradable organic semiconducting polymer (PTZ) nanoprobes emitting a peak at ∼1650 nm in H2O. PTZ nanoprobes enable ultrahigh-resolution imaging of near-single-cell cancer (as few as approximately 20 cells), tiny blood vessels (∼100 μm), and ultradeep-seated bone marrow in vivo. Furthermore, the PTZ permits the development of NIR-IIbc molecular probes for ultrahigh-resolution imaging of deep-seated orthotopic liver tumors as small as ∼1.5 mm in vivo. Importantly, PTZ-based probes are biodegradable and can be cleared through hepatobiliary and renal pathways within 18 days, alleviating long-term toxicity concerns. Our work reveals the molecular design toward ultrabright organic NIR-IIbc fluorophores and highlights new opportunities for high-resolution deep-tissue imaging.