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Here, using structurally defined DMA\u2010PEG\n                    <jats:sub>16<\/jats:sub>\n                    \u2010OMe as a discrete PEG\u2010lipid model and conventional DMA\u2010PEG\n                    <jats:sub>2k<\/jats:sub>\n                    \u2010OMe as a comparator, we show that Zn\n                    <jats:sup>2+<\/jats:sup>\n                    addition produces a concentration\u2010dependent redistribution of organ\u2010associated LNP\u2010mediated mRNA expression from the liver toward the spleen. This redistribution was most pronounced in the PEG\n                    <jats:sub>16<\/jats:sub>\n                    formulation and was not observed to the same extent in the conventional PEG\n                    <jats:sub>2k<\/jats:sub>\n                    formulation, supporting PEG\u2010lipid interfacial architecture as an important determinant of the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent response. Mechanistically, Zn\n                    <jats:sup>2+<\/jats:sup>\n                    is associated with protein\u2010corona remodeling, including enrichment of apolipoprotein H (ApoH; \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u2010glycoprotein I), a corona component previously linked to splenic tropism, together with reduced inflammatory transcriptional activation. In a prophylactic B16F10\u2010OVA\u2010luc challenge model, Zn@PEG\n                    <jats:sub>16<\/jats:sub>\n                    \u2010LNP treatment was associated with improved tumor control, higher total serum IgG and IgG1 signals, and stronger SIINFEKL\u2010responsive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell responses. Together, these findings identify PEG\u2010lipid interfacial architecture and Zn\n                    <jats:sup>2+<\/jats:sup>\n                    incorporation as a simple formulation strategy for spleen\u2010directed mRNA delivery.\n                  <\/jats:p>","DOI":"10.1002\/smll.75877","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:49:02Z","timestamp":1790005742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PEG\u2010Lipid Interfacial Architecture Enables Zn\n                    <sup>2+<\/sup>\n                    \u2010Dependent Redistribution of LNP\u2010Mediated mRNA Expression Toward the Spleen"],"prefix":"10.1002","author":[{"given":"Bing","family":"Shao","sequence":"first","affiliation":[{"name":"Hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of China  Hefei China"},{"name":"Department of 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Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of the University of Science and Technology of China  Hefei China"},{"name":"State Key Laboratory of Precision and Intelligent Chemistry University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of the University of Science and Technology of China  Hefei China"},{"name":"State Key Laboratory of Precision and Intelligent Chemistry University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of the University of 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