癌症疫苗
癌症
介绍(产科)
信使核糖核酸
纳米颗粒
抗原
抗原呈递
医学
免疫学
化学
免疫系统
免疫疗法
纳米技术
材料科学
生物化学
基因
T细胞
内科学
放射科
作者
Jiaqi Lei,Shaolong Qi,Xinyang Yu,Xianhua Gao,Kai Yang,Xueyi Zhang,Bin Bai,Yunxuan Feng,Meixin Lu,Yangfan Wang,Hongjian Li,Guocan Yu
标识
DOI:10.1002/anie.202318515
摘要
Insufficient accumulation of lipid nanoparticles (LNPs)‐based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor‐mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs‐Man). Intramuscular injection of mRNA vaccine (STLNPs‐Man@mRNAOVA) results in a four‐fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs‐Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one‐fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs‐Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T‐lymphocyte‐associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.
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