An efficient antitumor immune response relies on multiple cells-based process including tumor cells-targeted immunogenicity increment, dendritic cells (DCs)-targeted vaccine delivery and T cells-mediated tumor elimination. Only limited immune efficacy could be achieved by strengthening the function of single type of cells. Therefore, building an effective immunotherapeutic nanoplatform by simultaneously modulating the functions of multiple cells involved in immune process is urgently demanded. However, it is challenging to modulate multiple cells since the on-demand delivery of diverse agents to different cells is restricted by inherent different target sites. Herein, as a proof of concept, dual tailor-made metal organic framework (MOF) nanoparticles based on zeolitic imidazolate framework-8 (ZIF-8) are designed to comprehensively enhance the immunotherapy via the spatiotemporal cooperation of various therapeutic agents including photothermal agent IR820, adjuvant imiquimod (R837) and immunomodulator 1-methyl-d-tryptophan (1 MT). On one hand, IR820@ZIF-8 is modified with hyaluronic acid for realizing tumor-targeted photothermal therapy, accompanied with the release of tumor antigens. On the other hand, (R837+1 MT)@ZIF-8 is modified with mannan for achieving DCs-targeted immune amplification. The synergistic tumor cells-targeted treatment and DCs-targeted immunomodulation can efficiently overcome two major obstacles in immunotherapy: inadequate activation of immune response and immune evasion, offering powerful platform against invasive malignancy and rechallenged tumors.

有效的抗肿瘤免疫应答依赖于多种细胞为基础的过程，包括靶向肿瘤细胞的免疫原性增加，靶向树突细胞（DC）的疫苗递送以及T细胞介导的肿瘤消除。通过增强单一类型细胞的功能只能获得有限的免疫功效。因此，迫切需要通过同时调节参与免疫过程的多个细胞的功能来构建有效的免疫治疗纳米平台。然而，调节多种细胞是有挑战性的，因为将多种试剂按需递送至不同细胞受到固有的不同靶位点的限制。在此，作为概念证明，d-色氨酸（1 MT）。一方面，IR820 @ ZIF-8用透明质酸修饰，可实现针对肿瘤的光热疗法，并伴随释放肿瘤抗原。另一方面，用甘露聚糖修饰了（R837 + 1 MT）@ ZIF-8，以实现靶向DC的免疫扩增。靶向肿瘤细胞的协同治疗和靶向DCs的免疫调节可以有效克服免疫治疗中的两个主要障碍：免疫反应激活不足和免疫逃避，为侵袭性恶性肿瘤和再发肿瘤提供了强大的平台。