Site-specific MOF-based immunotherapeutic nanoplatforms via synergistic tumor cells-targeted treatment and dendritic cells-targeted immunomodulation.

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.