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

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 (alpha PD-L1) antibody, alpha PD-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 alpha PD-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, alpha PD-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.