A novel PD-L1 targeting peptide self-assembled nanofibers for sensitive tumor imaging and photothermal immunotherapy in vivo

Programmed death 1 (PD-1) and its ligand PD-L1 are two typical immune checkpoints. Antibody-based immune checkpoint blockade (ICB) strategy targeting PD-1/PD-L1 achieved a significant therapeutic effect on cancer. However, due to the impenetrability of antibody drugs and the occurrence of immune-related adverse events, only a minority of patients benefit from this treatment. Peptides multimerization has been widely proved to be an effective method to improve receptor binding affinity through a multivalent synergistic effect. In this study, we report a novel peptide-aggregation-induced emission (AIE) hybrid supramolecular TAP, which can self-assemble into nanofibers through non-covalent interactions such as hydrogen bonds, with a specific nanomolar affinity to PD-L1 in vivo and in vitro. Combined with near-infrared agents, it can be used for tumor imaging and photothermal therapy, which enables photothermal ablation of cancer cells for generating tumor-associated antigen (TAA) and triggering a series of immunological events. Collectively, our work suggests that synthetic self-assembled peptide nanofibers can be developed as attractive platforms for active photothermal immunotherapies against cancer.