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DOI | 10.1073/pnas.2005191118 |
Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through toll-like receptor 4 signaling | |
Zhang H.; You X.; Wang X.; Cui L.; Wang Z.; Xu F.; Li M.; Yang Z.; Liu J.; Huang P.; Kang Y.; Wu J.; Xia X. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:6 |
英文摘要 | Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Cancer immunotherapy; Lipid-like material; mRNA nanovaccine; Self-adjuvant; TLR4 |
语种 | 英语 |
scopus关键词 | c1 nanoparticel; lipid nanoparticle; RNA vaccine; toll like receptor 4; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antigen expression; antineoplastic activity; Article; cancer immunotherapy; cancer prevention; controlled study; drug accumulation; drug delivery system; drug design; drug distribution; drug efficacy; drug screening; drug structure; female; in vitro study; in vivo study; mouse; nonhuman; priority journal; protein expression; TLR signaling; wild type |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180692 |
作者单位 | State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006, China; State Key Laboratory for Diagnostic and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China |
推荐引用方式 GB/T 7714 | Zhang H.,You X.,Wang X.,et al. Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through toll-like receptor 4 signaling[J],2021,118(6). |
APA | Zhang H..,You X..,Wang X..,Cui L..,Wang Z..,...&Xia X..(2021).Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through toll-like receptor 4 signaling.Proceedings of the National Academy of Sciences of the United States of America,118(6). |
MLA | Zhang H.,et al."Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through toll-like receptor 4 signaling".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021). |
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