ICG-labeled PD-L1-antagonistic affibody dimer for tumor imaging and enhancement of tumor photothermal-immunotherapy

In clinical practice, tumor-targeting diagnosis and immunotherapy against programmed death ligand 1 (PD-L1) have a significant impact. In this research, a PD-L1-antagonistic affibody dimer (Z_PD-L1) was successfully prepared through Escherichia coli expression system, and conjugated with the photosensitizer of ICG via N-hydroxysuccinimide (NHS) ester to develop a novel tumor-targeting agent (ICG-Z_PD-L1) for both tumor imaging diagnosis and photothermal-immunotherapy simultaneously. In vitro, Z_PD-L1 could specifically bind to PD-L1-positive LLC and MC38 tumor cells, and ICG-Z_PD-L1-mediated photothermal therapy (PTT) also showed excellent phototoxicity to these tumor cells. In vivo, ICG-Z_PD-L1 selectively enriched into the PD-L1-positive MC38 tumor tissues, and the high-contrast optical imaging of tumors was obtained. ICG-Z_PD-L1-mediated PTT exhibited a potent anti-tumor effect in vivo due to its remarkable photothermal properties. Furthermore, ICG-Z_PD-L1-mediated PTT significantly induced the immunogenic cell death (ICD) of primary tumors, promoted maturation of dendritic cells (DCs), up-regulated anti-tumor immune response, enhanced immunotherapy, and superiorly inhibited the growth of metastatic tumors. In addition, ICG-Z_PD-L1 showed favorable biosafety throughout the brief duration of treatment. In summary, these results suggest that ICG-Z_PD-L1 is a multifunctional tumor-targeting drug integrating tumor imaging diagnosis and photothermal-immunotherapy, and has great guiding significance for the diagnosis and treatment of clinical PD-L1-positive tumor patients.