A Versatile 980 nm Absorbing Aggregation‐Induced Emission Luminogen for NIR‐II Imaging‐Guided Synergistic Photo‐Immunotherapy Against Advanced Pancreatic Cancer

Abstract To address urgent tasks in the treatment of advanced deep‐seated tumors, a 980 nm absorbing agent with aggregation‐induced emission tendency, namely TPE‐BT‐BBTD, which simultaneously possesses the longest absorption wavelength among all the reported AIE molecules is developed. The functionality of deep near‐infrared‐II fluorescence imaging (NIR‐II FLI) and outstanding photothermal performance is well‐tailored for advanced pancreatic cancer treatment. With the covalent attachment of the programmed death‐ligand 1 (αPD‐L1) antibody, αPD‐L1@TPE‐BT‐BBTD nanoparticles show precise tumor targeting and excellent immunosuppression reversal ability. Following local photothermal therapy, immunogenic tumor vaccination is induced to trigger the infiltration of cytotoxic T lymphocytes (CTLs) in tumors. With the decreased FoxP3 + Treg cells and M2‐like macrophages that are reversed by αPD‐L1, CTLs activity is further enhanced with more production of granzyme B (GrB), which much accurately leads to tumor apoptosis and effectively suppressed spontaneous metastases. Overall, αPD‐L1@TPE‐BT‐BBTD nanoparticles based NIR‐II FLI‐mediated photo‐immunotherapy is able to significantly improve the control of primary tumor and metastasis in the treatment of advanced deep‐seated tumors.