免疫疗法
纳米团簇
材料科学
癌症研究
内化
渗透(HVAC)
肿瘤微环境
细胞外基质
单克隆抗体
癌症免疫疗法
免疫系统
抗体
医学
纳米技术
免疫学
细胞生物学
化学
生物
肿瘤细胞
细胞
生物化学
复合材料
作者
Xingjie Hu,Ni‐Yuan Zhang,Da‐Yong Hou,Zhijia Wang,Man‐Di Wang,Li Yi,Zhiguo J. Song,Jingshan Liang,Xiangpeng Li,Hong‐Wei An,Wanhai Xu,Hao Wang
标识
DOI:10.1002/adma.202303831
摘要
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.
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