Since antigen and adjuvant are rapid clearance in vivo,insufficient delivery to induce dendritic cells(DCs)maturation and cross-presentation,as well as limited migration efficiency of DCs to secondary lymph or-gans,greatly hinders the development of DCs-based immunotherapy.Herein,PCL-PEG-PCL polymersomes(PCEP-PS)as antigen and adjuvants delivery nanoplatforms(IMO-PS)were well-designed,which can elec-trostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release,incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activat-ing synergistic immune responses via different signaling pathways.The IMO-PS significantly improved antigen uptake,promoted DCs maturation and cytokines production.DCs treated with IMO-PS could en-hance migration into draining lymphoid nodes,and eventually induced antigen-specific CD8+and CD4+T cell responses and OVA-specific cytotoxic T lymphocyte(CTL)responses.Prophylactic vaccination of EG7-OVA tumor-bearing mice by IMO-PS+DCs significantly extended tumor-free time,effectively sup-pressed tumor growth,and greatly extended median survival time.The strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.

Hanyong Wang;Xinyu Yang;Chunyan Hu;Chenlu Huang;Hai Wang;Dunwan Zhu;Linhua Zhang

Tianjin Key Laboratory of Biomedical Materials,Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300192,China

中国化学快报（英文版）

[1]Hanyong Wang;Xinyu Yang;Chunyan Hu;Chenlu Huang;Hai Wang;Dunwan Zhu;Linhua Zhang-.Programmed polymersomes with spatio-temporal delivery of antigen and dual-adjuvants for efficient dendritic cells-based cancer immunotherapy)[J].中国化学快报（英文版）,2022(09):4179-4184

polymersomes,PCEP,trostatically,ligate,activat,CD8+and,EG7,PS+DCs

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