Manganese-based microcrystals equipped with Ythdf1-targeted biomimetic nanovaccines for reinforced dendritic cell spatiotemporal orchestration
Feng Liu, Lulu Tan, Zheng Dai, Yang Wang, Lei Huang, Yang Zhang, Qian Cheng, Xin Li, Miao‐Deng Liu, Lin Wang, Zheng Wang
Abstract
Undesired dendritic cell (DC) spatiotemporal orchestration and innate immune stimulation severely dampens anti-tumor efficacy of cancer vaccines. Here, we develop a manganese-based (Mn2+) metal-organic framework (MOF) microcrystal equipped with Ythdf1-targeted biomimetic nanovaccines to create an in situ proinflammatory immune niche for augmented DC spatiotemporal orchestration. The bimetallic MOF microcrystal serves as a self-adjuvanting delivery platform that cannot only gradually release tumor-associated antigens and Mn2+, but also create an in situ immune niche for DC spatiotemporal orchestration including recruitment (particularly for DC1s, cross-presenting antigens to CD8+ T cells), activation, and lymph node migration. Benefitting from the Mn2+-mediated cGAS-STING activation together with Ythdf1 downregulation-induced antigen cross-presentation reinforcement, the vaccines elicit robust prophylactic efficacy for delaying B16-OVA and MC38 tumor occurrence, and show potent therapeutic efficacy for suppressing postoperative MC38 tumor recurrence and metachronous liver metastasis. Our study provides a versatile and powerful approach for fabricating personalized scaffold cancer vaccines.