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Toll\u2010like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7\/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2\u20103L) remarkably enhances the translation efficiency of mRNA and a \u03b2\u2010cyclodextrin (\u03b2\u2010CD)\u2010modified ionizable lipid (Lip\u2010CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host\u2013guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next\u2010generation delivery system in the development of mRNA vaccines with high efficacy.<\/jats:p>","DOI":"10.1002\/adma.202311574","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T03:31:52Z","timestamp":1709523112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Supramolecular Lipid Nanoparticles Based on Host\u2013Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Shaolong","family":"Qi","sequence":"first","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Department of Chemistry Tsinghua University Beijing 100084 P. R. 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