An In Vivo Self-Assembled Bispecific Nanoblocker for Enhancing Tumor Immunotherapy

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 45 vom: 18. Nov., Seite e2303831
1. Verfasser: Hu, Xing-Jie (VerfasserIn)
Weitere Verfasser: Zhang, Ni-Yuan, Hou, Da-Yong, Wang, Zhi-Jia, Wang, Man-Di, Yi, Li, Song, Zhang-Zhi, Liang, Jian-Xiao, Li, Xiang-Peng, An, Hong-Wei, Xu, Wanhai, Wang, Hao
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article biomaterials bispecific nanoblockers immunotherapies peptides self-assembly B7-H1 Antigen Antibodies, Bispecific
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520 |a Anti-PD-L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T-cells activation. However, the excessive accumulation of extracellular matrix components induced by unsatisfactory T-cells infiltration and poor tumor penetration of antibodies make it challenging to realize efficient tumor immunotherapy. Herein, a peptide-based bispecific nanoblocker (BNB) strategy is reported for in situ construction of CXCR4/PD-L1 targeted nanoclusters on the surface of tumor cells that are capable of boosting T-cells infiltration through CXCR4 blockage and enhancing T-cells activation by PD-L1 occupancy, ultimately realizing high-performance tumor immunotherapy. Briefly, the BNB strategy selectively recognizes and bonds CXCR4/PD-L1 with deep tumor penetration, which rapidly self-assembles into nanoclusters on the surface of tumor cells. Compared to the traditional bispecific antibody, BNB exhibits an intriguing metabolic behavior, that is, the elimination half-life (t1/2 ) of BNB in the tumor is 69.3 h which is ≈50 times longer than that in the plasma (1.4 h). The higher tumor accumulation and rapid systemic clearance overcome potential systemic side effects. Moreover, the solid tumor stress generated by excessive extracellular matrix components is substantially reduced to 44%, which promotes T-cells infiltration and activation for immunotherapy efficacy. Finally, these findings substantially strengthen and extend clinical applications of PD-1/PD-L1 immunotherapy 
650 4 |a Journal Article 
650 4 |a biomaterials 
650 4 |a bispecific nanoblockers 
650 4 |a immunotherapies 
650 4 |a peptides 
650 4 |a self-assembly 
650 7 |a B7-H1 Antigen  |2 NLM 
650 7 |a Antibodies, Bispecific  |2 NLM 
700 1 |a Zhang, Ni-Yuan  |e verfasserin  |4 aut 
700 1 |a Hou, Da-Yong  |e verfasserin  |4 aut 
700 1 |a Wang, Zhi-Jia  |e verfasserin  |4 aut 
700 1 |a Wang, Man-Di  |e verfasserin  |4 aut 
700 1 |a Yi, Li  |e verfasserin  |4 aut 
700 1 |a Song, Zhang-Zhi  |e verfasserin  |4 aut 
700 1 |a Liang, Jian-Xiao  |e verfasserin  |4 aut 
700 1 |a Li, Xiang-Peng  |e verfasserin  |4 aut 
700 1 |a An, Hong-Wei  |e verfasserin  |4 aut 
700 1 |a Xu, Wanhai  |e verfasserin  |4 aut 
700 1 |a Wang, Hao  |e verfasserin  |4 aut 
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773 1 8 |g volume:35  |g year:2023  |g number:45  |g day:18  |g month:11  |g pages:e2303831 
856 4 0 |u http://dx.doi.org/10.1002/adma.202303831  |3 Volltext 
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