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

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Abstract

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.

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Acknowledgements

This work was supported financially by the National Natural Science Foundation of China (Nos. 32027801, 81801766, 21775031, and 31870992), the Strategic Priority Research Program of Chinese Academy of Sciences (Nos. XDB36000000 and XDB38010400), Foundation of Chongqing Municipal Education Commission (No. HZ2021006), CAS-JSPS (No. GJHZ2094), Fujian Medical University Foundation for the Introduction of Talents (Nos. XRCZX2017020, XRCZX2019005, and XRCZX2019018), and the Joint Funds for the innovation of science and Technology Fujian Province (No. 2019Y9001).

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Correspondence to Dong Wang, Zhiyuan Hu or Zihua Wang.

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

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Fu, L., Zhang, J., Wu, C. et al. A novel PD-L1 targeting peptide self-assembled nanofibers for sensitive tumor imaging and photothermal immunotherapy in vivo. Nano Res. 15, 7286–7294 (2022). https://doi.org/10.1007/s12274-022-4331-5

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