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Here, natural cholesterol analogs are screened to assemble self\u2010adjuvant lipid nanoparticles (LNPs) for antigens tagging tumor cells and dendritic cells (DC) activation. First, a library of ginsenosides are collected, and then screened according to their anti\u2010tumor immunity. Then, ginsenoside\u2010Rg3 based\u2010LNPs loaded with antigens (Rg3\u2010LNPs) are identified as the optimal formulation by investigating the physicochemical and biological properties. Finally, Rg3\u2010LNPs and granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) are co\u2010loaded into a macroporous hydrogel for long\u2010term immune response. Rg3\u2010LNPs could accumulate into both tumors and LNs. Rg3\u2010LNPs targeted tumor cells with high glucose transporter\u20101 expression via the targeting ligand Rg3, and anchored antigens on the tumor cell surface, thus promoting the recognition of CTL to tumor cells; Rg3\u2010LNPs can accumulate into the LNs to promote DC activation and antigen presentation, thus stimulating CTL activation. Besides, Rg3, as an adjuvant, cooperated with GM\u2010CSF to remodel the tumor microenvironment, thus promoting the killing of CTL to tumor cells. Collectively, this work highlights the importance of tagging antigens to tumor cells in tumor vaccine and has great clinical value for immune\u2010escaping tumors.<\/jats:p>","DOI":"10.1002\/adma.202419182","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T06:08:02Z","timestamp":1745647682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Screening Natural Cholesterol Analogs to Assemble Self\u2010Adjuvant Lipid Nanoparticles for Antigens Tagging Guided Therapeutic Tumor Vaccine"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7142-781X","authenticated-orcid":false,"given":"Shuang","family":"Liang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Key Laboratory of Chemical Biology (Ministry of Education) NMPA Key Laboratory for Technology Research and Evaluation of Drug Products State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Qilu Hospital of Shandong University The Second Hospital Cheeloo College of Medicine Shandong University  44 Wenhua Xi Road Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Key Laboratory of Chemical Biology (Ministry of Education) NMPA Key Laboratory for Technology Research and Evaluation of Drug Products State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Qilu Hospital of Shandong University The Second Hospital Cheeloo College of Medicine Shandong University  44 Wenhua Xi Road Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunli","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Key Laboratory of Chemical Biology (Ministry of Education) 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The Second Hospital Cheeloo College of Medicine Shandong University  44 Wenhua Xi Road Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiqiang","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Key Laboratory of Chemical Biology (Ministry of Education) NMPA Key Laboratory for Technology Research and Evaluation of Drug Products State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Qilu Hospital of Shandong University The Second Hospital Cheeloo College of Medicine Shandong University  44 Wenhua Xi Road Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zipeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong 250062 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