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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.
Keir, M. E.; Butte, M. J.; Freeman, G. J.; Sharpe, A. H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 2008, 26, 677–704.
Tumeh, P. C.; Harview, C. L.; Yearley, J. H.; Shintaku, I. P.; Taylor, E. J. M.; Robert, L.; Chmielowski, B.; Spasic, M.; Henry, G.; Ciobanu, V. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014, 515, 568–571.
Iwai, Y.; Ishida, M.; Tanaka, Y.; Okazaki, T.; Honjo, T.; Minato, N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA 2002, 99, 12293–12297.
Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264.
Postow, M. A.; Callahan, M. K.; Wolchok, J. D. Immune checkpoint blockade in cancer therapy. J. Clin. Oncol. 2015, 33, 1974–1982.
Sharma, P.; Allison, J. P. The future of immune checkpoint therapy. Science 2015, 348, 56–61.
Muttenthaler, M.; King, G. E.; Adams, D. J.; Alewood, P. F. Trends in peptide drug discovery. Nat. Rev. Drug Discov. 2021, 20, 309–325.
Cooper, B. M.; Iegre, J.; O'Donovan, D. H.; Halvarsson, M. O.; Spring, D. R. Peptides as a platform for targeted therapeutics for cancer: Peptide-drug conjugates (PDCs). Chem. Soc. Rev. 2021, 50, 1480–1494.
Xing, P. Y.; Zhao, Y. L. Multifunctional nanoparticles self-assembled from small organic building blocks for biomedicine. Adv. Mater. 2016, 28, 7304–7339.
Qi, G. B.; Gao, Y. J.; Wang, L.; Wang, H. Self-assembled peptide-based nanomaterials for biomedical imaging and therapy. Adv. Mater. 2018, 30, 1703444.
Habibi, N.; Kamaly, N.; Memic, A.; Shafiee, H. Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery. Nano Today 2016, 11, 41–60.
Li, J.; Wang, J. Q.; Zhao, Y. R.; Zhou, P.; Carter, J.; Li, Z. Y.; Waigh, T. A.; Lu, J. R.; Xu, H. Surfactant-like peptides: From molecular design to controllable self-assembly with applications. Coord. Chem. Rev. 2020, 421, 213418.
Fleming, S.; Ulijn, R. V. Design of nanostructures based on aromatic peptide amphiphiles. Chem. Soc. Rev. 2014, 43, 8150–8177.
Moore, A. N.; Hartgerink, J. D. Self-assembling multidomain peptide nanofibers for delivery of bioactive molecules and tissue regeneration. Acc. Chem. Res. 2017, 50, 714–722.
Wang, Y.; An, Y. X.; Shmidov, Y.; Bitton, R.; Deshmukh, S. A.; Matson, J. B. A combined experimental and computational approach reveals how aromatic peptide amphiphiles self-assemble to form ion-conducting nanohelices. Mater. Chem. Front. 2020, 4, 3022–3031.
Li, S. K.; Zhang, W. J.; Xing, R. R.; Yuan, C. Q.; Xue, H. D.; Yan, X. H. Supramolecular nanofibrils formed by coassembly of clinically approved drugs for tumor photothermal immunotherapy. Adv. Mater. 2021, 33, 2100595.
Li, X. S.; Lovell, J. F.; Yoon, J.; Chen, X. Y. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol. 2020, 17, 657–674.
Huang, X. Y.; Lu, Y.; Guo, M. X.; Du, S. Y.; Han, N. Recent strategies for nano-based PTT combined with immunotherapy: From a biomaterial point of view. Theranostics 2021, 11, 7546–7569.
Xu, P.; Liang, F. Nanomaterial-based tumor photothermal immunotherapy. Int. J. Nanomed. 2020, 15, 9159–9180.
Delfi, M.; Sartorius, R.; Ashrafizadeh, M.; Sharifi, E.; Zhang, Y. P.; De Berardinis, P.; Zarrabi, A.; Varma, R. S.; Tay, F. R.; Smith, B. R. et al. Self-assembled peptide and protein nanostructures for anti-cancer therapy: Targeted delivery, stimuli-responsive devices and immunotherapy. Nano Today 2021, 38, 101119.
Shang, T. Y.; Yu, X. Y.; Han, S. S.; Yang, B. Nanomedicine-based tumor photothermal therapy synergized immunotherapy. Biomater. Sci. 2020, 8, 5241–5259.
Zhang, R. Y.; Duan, Y. K.; Liu, B. Recent advances of AIE dots in NIR imaging and phototherapy. Nanoscale 2019, 11, 19241–19250.
Chen, C.; Ni, X.; Jia, S. R.; Liang, Y.; Wu, X. L.; Kong, D. L.; Ding, D. Massively evoking immunogenic cell death by focused mitochondrial oxidative stress using an AIE luminogen with a twisted molecular structure. Adv. Mater. 2019, 31, 1904914.
Li, J.; Gao, H. Q.; Liu, R. H.; Chen, C.; Zeng, S.; Liu, Q.; Ding, D. Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death. Sci. China Chem. 2020, 63, 1428–1434.
Liao, Y. H.; Wang, R. L.; Wang, S. Z.; Xie, Y. F.; Chen, H. H.; Huang, R. J.; Shao, L. Q.; Zhu, Q. H.; Liu, Y. S. Highly efficient multifunctional organic photosensitizer with aggregation-induced emission for in vivo bioimaging and photodynamic therapy. ACS Appl. Mater. Interfaces 2021, 13, 54783–54793.
Dai, J.; Li, Y. H.; Long, Z.; Jiang, R. M.; Zhuang, Z. Y.; Wang, Z. M.; Zhao, Z. J.; Lou, X. D.; Xia, F.; Tang, B. Z. Efficient near-infrared photosensitizer with aggregation-induced emission for imaging-guided photodynamic therapy in multiple xenograft tumor models. ACS Nano 2020, 14, 854–866.
Li, X. S.; Kim, J.; Yoon, J.; Chen, X. Y. Cancer-associated, stimuli-driven, turn on theranostics for multimodality imaging and therapy. Adv. Mater. 2017, 29, 1606857.
Qian, Y. X.; Wang, W. Z.; Wang, Z. H.; Han, Q. J.; Jia, X. Q.; Yang, S.; Hu, Z. Y. Switchable probes: pH-triggered and VEGFR2 targeted peptides screening through imprinting microarray. Chem. Commun. 2016, 52, 5690–5693.
Wang, A. H.; Cui, L. Y.; Debnath, S.; Dong, Q. Q.; Yan, X. H.; Zhang, X.; Ulijn, R. V.; Bai, S. Tuning supramolecular structure and functions of peptide bola-amphiphile by solvent evaporation-dissolution. ACS Appl. Mater. Interfaces 2017, 9, 21390–21396.
Wang, J.; Liu, K.; Yan, L. Y.; Wang, A. H.; Bai, S.; Yan, X. H. Trace solvent as a predominant factor to tune dipeptide self-assembly. ACS Nano 2016, 10, 2138–2143.
Yang, Y. P. Cancer immunotherapy: Harnessing the immune system to battle cancer. J. Clin. Invest. 2015, 125, 3335–3337.
Etezadi, D.; Warner IV, J. B.; Ruggeri, F. S.; Dietler, G.; Lashuel, H. A.; Altug, H. Nanoplasmonic mid-infrared biosensor for in vitro protein secondary structure detection. Light Sci. Appl. 2017, 6, e17029.
Raymond, D. M.; Nilsson, B. L. Multicomponent peptide assemblies. Chem. Soc. Rev. 2018, 47, 3659–3720.
Castelletto, V.; Kirkham, S.; Hamley, I. W.; Kowalczyk, R.; Rabe, M.; Reza, M.; Ruokolainen, J. Self-assembly of the toll-like receptor agonist macrophage-activating lipopeptide MALP-2 and of its constituent peptide. Biomacromolecules 2016, 17, 631–640.
Zhou, X. M.; Zuo, C.; Li, W. Q.; Shi, W. W.; Zhou, X. W.; Wang, H. F.; Chen, S. M.; Du, J. F.; Chen, G. Y.; Zhai, W. J. et al. A novel D-peptide identified by mirror-image phage display blocks TIGIT/PVR for cancer immunotherapy. Angew. Chem. , Int. Ed. 2020, 59, 15114–15118.
Xu, X. L.; Deng, G. J.; Sun, Z. H.; Luo, Y.; Liu, J. K.; Yu, X. H.; Zhao, Y.; Gong, P.; Liu, G. Z.; Zhang, P. F. et al. A biomimetic aggregation-induced emission photosensitizer with antigen-presenting and hitchhiking function for lipid droplet targeted photodynamic immunotherapy. Adv. Mater. 2021, 33, 2102322.
Guo, J. C.; An, Q.; Guo, M. Y.; Xiao, Y. T.; Li, B.; Gao, F. E.; Wang, Y. Q.; Li, J. Y.; Wang, Y. L.; Liu, Y. et al. Oxygen-independent free radical generation mediated by core–shell magnetic nanocomposites synergizes with immune checkpoint blockade for effective primary and metastatic tumor treatment. Nano Today 2021, 36, 101024.
Qian, Y. X.; Wang, Y. H.; Jia, F.; Wang, Z. H.; Yue, C. Y.; Zhang, W. K.; Hu, Z. Y.; Wang, W. Z. Tumor-microenvironment controlled nanomicelles with AIE property for boosting cancer therapy and apoptosis monitoring. Biomaterials 2019, 188, 96–106.
Conde, J.; Oliva, N.; Zhang, Y.; Artzi, N. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model. Nat. Mater. 2016, 15, 1128–1138.