抗原
佐剂
树突状细胞
免疫疗法
癌症免疫疗法
免疫系统
抗原呈递
免疫学
抗原提呈细胞
聚合物囊泡
癌症研究
化学
T细胞
医学
聚合物
有机化学
两亲性
共聚物
作者
Hanyong Wang,Xinyu Yang,Cnyan hu,Chenlu Huang,Hai Wang,Dunwan Zhu,Linhua Zhang
标识
DOI:10.1016/j.cclet.2022.02.022
摘要
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 organs, 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 electrostatically 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 activating 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 enhance 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 suppressed 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.
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