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Here, we report a self\u2010assembling nanovaccine platform based on dendritic lipopeptides (DLPs) that integrate delivery and immune\u2010stimulation through a structurally defined design. DLPs are constructed by conjugating structurally optimized lipid tails to second\u2010generation lysine\u2010 or arginine\u2010rich dendritic scaffolds. Systematic engineering of the lipid domain allows for precise fine\u2010tuning of the amphiphilic structure, yielding molecular candidates with significantly enhanced TLR2\/4 agonist activity. These structures facilitate antigen uptake and cross\u2010presentation by APCs in a spatiotemporally regulated manner. Co\u2010assembly with lipidated peptide antigens and a lipid\u2010modified TLR7\/8 agonist yields nanoscale vaccines capable of orchestrating synergistic multi\u2010pattern recognition receptor (PRR) activation. In murine melanoma and colorectal tumor models, these nanovaccines elicit robust cytotoxic T lymphocyte responses, enhance antigen\u2010specific killing by up to 40%, and induce significant tumor regression. This work presents a chemically defined, modular nanoplatform that mimics key features of pathogen\u2010like immunity and provides a rational strategy for engineering minimalist cancer vaccines with high efficacy and translational potential.<\/jats:p>","DOI":"10.1002\/adma.73533","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:48:47Z","timestamp":1780379327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dendritic Lipopeptide Nanovaccines Orchestrate Multi\u2010Pattern Recognition Receptors Activation and Potentiate Antitumor Immunity"],"prefix":"10.1002","volume":"38","author":[{"given":"Muhetaerjiang","family":"Mamuti","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of High Performance Polymer Materials &amp; Technology and State Key Laboratory of Analytical Chemistry For Life Science School of Chemistry Nanjing University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of High Performance Polymer Materials &amp; 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