An AlFu MOF nanoadjuvant functionalized with mannose for potential dendritic-cell targeting and dual TLR9–STING activation

Background Aluminum adjuvants remain the most widely used adjuvants in licensed vaccines. Their broader application, however, is restricted by local and systemic adverse effects and limited antigen compatibility, slowing vaccine development.Methods A nanoscale aluminum – fumarate metal – organic framework (AlFu‑MOF) was synthesized in water using Pluronic F127 and acetic acid. Based on this framework, a composite nanoadjuvant—(D)-mannose‑cTAT‑CpG@M@AlFu‑MOF (DCC@M@AlFu‑MOF) – was designed and characterized. The loading capacity for immunostimulatory cargos, including MSA‑2, CpG, cTAT, (D)-mannose, and OVA, was evaluated. Cellular uptake and immune activation of antigen‑presenting cells were tested in vitro. AlFu‑MOF displayed high loading efficiency and improved antigen availability. DCC@M@AlFu‑MOF promoted dendritic cell maturation and activation and also triggered the STING signaling pathway.Conclusion DCC@M@AlFu‑MOF is an aluminum‑based nanoadjuvant with potential dendritic cell‑targeting ability. It can coordinate innate immune signaling and shows promise for enhancing vaccine‑induced immune responses.