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However, current LNP formulations still require functional modifications to tailor them for therapeutic and vaccine applications. Recently, fifth component\u2010incorporated LNPs were developed to finely tune their functionality, including immunogenicity and organ\u2010targeting ability. Here, biphenyl\u2010structured amphiphilic PDL1 inhibitors are employed as a fifth component to modify LNPs. Amphiphilic PDL1 inhibitor\u2010incorporated, ALC0315\u2010based LNPs show higher lymph node targeting, with a 6.94\u2010fold increase in mRNA expression in the inguinal lymph node, thereby improving lymph node expansion and immune cell infiltration and, consequently, inducing greater mRNA vaccine efficacy. Furthermore, a consistent lymph node\u2010targeting effect of the fifth component\u2010containing LNP was observed across studies using the SM102\u2010based LNP formulation, suggesting its universality. In conclusion, this study demonstrates that PDL1 inhibitor\u2010incorporated fifth\u2010component LNP serves as a next\u2010generation platform for mRNA vaccines.<\/jats:p>","DOI":"10.1002\/advs.77923","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Checkpoint Inhibitor as a Fifth Component of Lipid Nanoparticles Enables Lymph Node\u2010Targeting and Augments mRNA Vaccine Efficacy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3991-635X","authenticated-orcid":false,"given":"Minki","family":"Ha","sequence":"first","affiliation":[{"name":"Laboratory of Practical Nanomedicine Department of Medical and Biological Sciences The Catholic University of Korea  Bucheon\u2010si Gyeonggi\u2010do Republic of 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