Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly ( < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

中文翻译：

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长期联合阻断 CXCR4 和 PD-L1 并体内重新组装以强化肿瘤干扰

负免疫调节信号（PD-L1、CXCR4等）和弱免疫原性导致免疫系统无法检测和破坏癌细胞。 CXCR4阻断促进T细胞肿瘤浸润并增加肿瘤对抗PD-L1治疗的敏感性。在这里，用抗 PD-L1 肽和 CXCR4 拮抗剂移植 (APAB) 构建了 pH 响应性重组纳米材料，并与光热疗法协同治疗黑色素瘤和乳腺肿瘤。自组装的 APAB 纳米粒子在肿瘤中积累，并响应酸性肿瘤微环境而迅速转化为纳米纤维，导致接枝治疗剂的暴露。由于聚集诱导保留 (AIR) 效应，APAB 能够在肿瘤细胞周围重新组装并保持稳定超过 96 小时，从而实现长期有效的 PD-L1 和 CXCR4 联合阻断。光热效率（ICG）诱导肿瘤细胞的免疫原性细胞死亡（ICD），从而有效提高免疫原性。联合疗法（ICG@APAB）可有效抑制黑色素瘤小鼠原发肿瘤（∼83.52%）和远处肿瘤（∼76.24%）的生长，并显着（<0.05）延长42天以上的生存时间。 4只T1模型小鼠肿瘤转移抑制实验显示，ICG@APAB几乎抑制了肺转移的发生，肿瘤中CD31、MMP-9和VEGF的表达水平分别降低了82.26%、90.45%和41.54%。体内重组策略将为未来的免疫疗法提供新的视角，并推动联合疗法的开发进入临床环境。