Multimodal Nanosheet Artificial Antibodies for Augmented Cancer Immunotherapy
TL;DR
Nanosheet artificial antibodies featuring unique tripeptide assembly phases selectively bound to PD-L1 with nanomolar affinity enabling effective inhibition of the PD-1/PD-L1 signaling pathway are presented, providing an effective therapeutic strategy for cancer treatment.
Abstract
Antibodies are widely employed to block the PD-1/PD-L1 immune-evasion pathway in cancer immunotherapy [1]. Nevertheless, antibody-based immune PD-L1 checkpoint blockade has often shown limited therapeutic efficacy in clinical cancer treatment. In addition, antibodies have additional limitations such as poor stability, long discovery time, and high cost [2]. Herein, we present a facile approach for creating nanosheet artificial antibodies with both PD-L1 inhibitory activity and photothermal therapeutic activity for augmented cancer immunotherapy. Tripeptides with a nitriloacetate-Cu group were spontaneously assembled on WS 2 or MoSe 2 nanosheets via coordinate bonding, producing a variety of nanosheet antibody mimics. Nanosheet artificial antibodies featuring unique tripeptide assembly phases selectively bound to PD-L1 with nanomolar affinity, thereby enabling effective inhibition of the PD-1/PD-L1 signaling pathway. Experimental and computational outcomes revealed that the recognition selectivity of the nanosheet artificial antibodies for PD-L1 stemmed from their multivalent hydrogen bonds and hydrophobic interactions with the PD-L1 epitope. The multimodal MoSe 2 nanosheet artificial antibody effectively killed tumor cells through PD-L1 blockade combined with a photothermal therapeutic effect. The multimodal nanosheet artificial antibody-based combination immunotherapy promoted the infiltration of antitumoral immune cells into solid tumors in mice, enhancing the immunotherapeutic efficacy compared with monoclonal antibody treatment. These nanosheet artificial antibodies provide an effective therapeutic strategy for cancer treatment. Reference [1] a) H. K. Binz, P. Amstutz, A. Pluckthun, Nat. Biotechnol. 2005 , 23, 1257; b) A. Ribas, J. D. Wolchok, Science , 2018 , 359 , 1350 [2] T. W. Kang, I. J. Hwang, S. Lee, S. J. Jeon, C. Choi, J. Han, Y. So, W. Son, H. Kim, C. S. Yang, J. H. Park, H. Lee, and J. H. Kim, Advanced Materials , 2021 , 2101376