Bionanoparticle-Based Delivery in Antihypertensive Vaccine Mediates DC Activation through Lipid-Raft Reorganization
Bionanoparticle-Based Delivery in Antihypertensive Vaccine Mediates DC Activation through Lipid-Raft Reorganization
复制标题
抗高血压疫苗中基于生物纳米颗粒的递送通过脂筏重组介导 DC 激活
DOI：
10.1002/adfm.202000346
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发表时间：
2020-05-01
影响因子：
19
通讯作者：
Han Dong，Dong
中科院分区：
文献类型：
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作者：
Hu Xiajun，xia;Chen Xiao，Xiao;Han Dong，Dong
生物纳米颗粒(BNPS)被广泛用作疫苗载体。与传统的蛋白质载体相比，BNPS表现出纳米结构，使其能够与生物界面样的细胞膜或膜域相互作用。以病毒样颗粒Qβ为载体，制备了一种降压疫苗ATR-NP。Qβ对树突状细胞(DC)等抗原提呈细胞(APC)具有很高的递送效率和免疫原性，其诱导的DC激活高度依赖于膜脂筏。进一步的研究表明，ATR-NP与木筏具有紧密的亲和力，它们之间的界面效应通过NP引起的膜曲率变化促进了膜相分离和FRAFT的积累。脂筏堆积扩张，膜内扩散减弱，有利于信号蛋白Src在脂筏中的分配。蛋白质的异质性划分意味着更强的信号转导的功能集中。总之，靶向和重组膜结构域，如脂筏，表明BNPS可以作为疫苗载体，是疫苗和其他免疫制剂设计的有效策略。
Bionanoparticles (BNPs) are widely used as vaccine carriers. Compared with classic protein carriers, BNPs exhibit nanostructures that enable them to interaction with biointerface‐like cell membrane or membrane domains. An antihypertensive vaccine ATR‐NP is produced based on a virus‐like particle (VLP) Qβ carrier. Qβ shows great delivery efficiency and immunogenicity to antigen‐presenting cells (APCs) such as dendritic cells (DCs), and DC activation induced by ATR‐NP is highly dependent on membrane lipid rafts. Further studies reveal that ATR‐NP exhibits tight affinity to rafts, and interface effects between them prompt membrane phase separation and raft accumulation through NP‐induced membrane curvature change. Lipid rafts are accumulated and expanded together with a decline of their diffusion in membrane, which benefits signaling protein Src partition in rafts. The heterogeneous protein partition implies functional centralization for stronger signal transduction. In conclusion, targeting and reorganizing membrane domains such as lipid rafts suggests BNPs could be used as vaccine carriers and is a potent strategy for vaccine and other immunological agent design.