{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T06:15:26Z","timestamp":1794118526744,"version":"4.8.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Biomed. Eng"],"DOI":"10.1038\/s41551-025-01577-4","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T10:02:44Z","timestamp":1766052164000},"page":"1828-1842","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5444-4078","authenticated-orcid":false,"given":"Yu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1322-2676","authenticated-orcid":false,"given":"Pingchuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4870-6882","authenticated-orcid":false,"given":"Zeyu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-9480","authenticated-orcid":false,"given":"Sijin","family":"Luozhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Laflin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaopeng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-0635","authenticated-orcid":false,"given":"Simian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamilton","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0967-1682","authenticated-orcid":false,"given":"Wenchao","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9863-6899","authenticated-orcid":false,"given":"Shaoyi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"1577_CR1","doi-asserted-by":"crossref","unstructured":"Liu, H. et al. Beyond the endosomal bottleneck: understanding the efficiency of mRNA\/LNP delivery. Adv. Funct. Mater. 34, 2404510 (2024).","DOI":"10.1002\/adfm.202404510"},{"key":"1577_CR2","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1016\/j.cell.2022.06.035","volume":"185","author":"MC Sellars","year":"2022","unstructured":"Sellars, M. C., Wu, C. J. & Fritsch, E. F. Cancer vaccines: building a bridge over troubled waters. Cell 185, 2770\u20132788 (2022).","journal-title":"Cell"},{"key":"1577_CR3","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/S1473-3099(22)00271-7","volume":"22","author":"AP Munro","year":"2022","unstructured":"Munro, A. P. et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial. Lancet Infect. Dis. 22, 1131\u20131141 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"1577_CR4","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","volume":"20","author":"B Pulendran","year":"2021","unstructured":"Pulendran, B., Arunachalam, S. P. & O\u2019Hagan, D. T. Emerging concepts in the science of vaccine adjuvants. Nat. Rev. Drug Discov. 20, 454\u2013475 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1577_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31485-z","volume":"13","author":"JS Rosa Duque","year":"2022","unstructured":"Rosa Duque, J. S. et al. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents. Nat. Commun. 13, 3700 (2022).","journal-title":"Nat. Commun."},{"key":"1577_CR6","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.3390\/ph16081088","volume":"16","author":"T Korzun","year":"2023","unstructured":"Korzun, T. et al. From bench to bedside: implications of lipid nanoparticle carrier reactogenicity for advancing nucleic acid therapeutics. Pharmaceuticals 16, 1088 (2023).","journal-title":"Pharmaceuticals"},{"key":"1577_CR7","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1577_CR8","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41551-023-01082-6","volume":"9","author":"B Li","year":"2025","unstructured":"Li, B. et al. Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA. Nat. Biomed. Eng. 9, 167\u2013184 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"1577_CR9","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/nbt.3298","volume":"33","author":"A Wittrup","year":"2015","unstructured":"Wittrup, A. et al. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat. Biotechnol. 33, 870\u2013876 (2015).","journal-title":"Nat. Biotechnol."},{"key":"1577_CR10","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3390\/vaccines9101089","volume":"9","author":"S Bauernfeind","year":"2021","unstructured":"Bauernfeind, S. et al. Association between reactogenicity and immunogenicity after vaccination with BNT162b2. Vaccines 9, 1089 (2021).","journal-title":"Vaccines"},{"key":"1577_CR11","doi-asserted-by":"publisher","first-page":"102499","DOI":"10.1016\/j.cbpa.2024.102499","volume":"81","author":"Y Zhao","year":"2024","unstructured":"Zhao, Y., Wang, Z. M., Song, D., Chen, M. & Xu, Q. Rational design of lipid nanoparticles: overcoming physiological barriers for selective intracellular mRNA delivery. Curr. Opin. Chem. Biol. 81, 102499 (2024).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"1577_CR12","doi-asserted-by":"publisher","first-page":"114416","DOI":"10.1016\/j.addr.2022.114416","volume":"188","author":"CH Albertsen","year":"2022","unstructured":"Albertsen, C. H. et al. The role of lipid components in lipid nanoparticles for vaccines and gene therapy. Adv. Drug Deliv. Rev. 188, 114416 (2022).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"1577_CR13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307800120","volume":"121","author":"S Chatterjee","year":"2024","unstructured":"Chatterjee, S., Kon, E., Sharma, P. & Peer, D. Endosomal escape: a bottleneck for LNP-mediated therapeutics. Proc. Natl Acad. Sci. USA 121, e2307800120 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307798120","volume":"121","author":"J Witten","year":"2024","unstructured":"Witten, J., Hu, Y., Langer, R. & Anderson, D. G. Recent advances in nanoparticulate RNA delivery systems. Proc. Natl Acad. Sci. USA 121, e2307798120 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR15","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1002\/adma.200901407","volume":"22","author":"S Jiang","year":"2010","unstructured":"Jiang, S. & Cao, Z. Ultralow-fouling, functionalizable, and hydrolyzable zwitterionic materials and their derivatives for biological applications. Adv. Mater. 22, 920\u2013932 (2010).","journal-title":"Adv. Mater."},{"key":"1577_CR16","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1038\/s41591-019-0601-5","volume":"25","author":"T Bai","year":"2019","unstructured":"Bai, T. et al. Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel. Nat. Med. 25, 1566\u20131575 (2019).","journal-title":"Nat. Med."},{"key":"1577_CR17","doi-asserted-by":"crossref","unstructured":"Luozhong, S. et al. A de novo strategy to improve pharmacokinetics of proteins from mRNA therapeutics via zwitterionic polypeptide fusion. J. Am. Chem. Soc. 146, 21245\u201321249 (2024).","DOI":"10.1021\/jacs.4c07903"},{"key":"1577_CR18","doi-asserted-by":"publisher","first-page":"20507","DOI":"10.1021\/jacs.2c09484","volume":"144","author":"Z Yuan","year":"2022","unstructured":"Yuan, Z. et al. Mitigating the immunogenicity of AAV-mediated gene therapy with an immunosuppressive phosphoserine-containing zwitterionic peptide. J. Am. Chem. Soc. 144, 20507\u201320513 (2022).","journal-title":"J. Am. Chem. Soc."},{"key":"1577_CR19","doi-asserted-by":"publisher","first-page":"eabc5442","DOI":"10.1126\/sciadv.abc5442","volume":"7","author":"D Dong","year":"2021","unstructured":"Dong, D. et al. High-strength and fibrous capsule-resistant zwitterionic elastomers. Sci. Adv. 7, eabc5442 (2021).","journal-title":"Sci. Adv."},{"key":"1577_CR20","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nbt.2580","volume":"31","author":"L Zhang","year":"2013","unstructured":"Zhang, L. et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat. Biotechnol. 31, 553\u2013556 (2013).","journal-title":"Nat. Biotechnol."},{"key":"1577_CR21","doi-asserted-by":"publisher","first-page":"6109","DOI":"10.1002\/anie.201100884","volume":"50","author":"K Zhou","year":"2011","unstructured":"Zhou, K. et al. Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells. Angew. Chem. Int. Ed. Engl. 50, 6109\u20136114 (2011).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"1577_CR22","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1016\/j.ymthe.2019.07.018","volume":"27","author":"EJ Sayers","year":"2019","unstructured":"Sayers, E. J. et al. Endocytic profiling of cancer cell models reveals critical factors influencing LNP-mediated mRNA delivery and protein expression. Mol. Ther. 27, 1950\u20131962 (2019).","journal-title":"Mol. Ther."},{"key":"1577_CR23","doi-asserted-by":"publisher","first-page":"2000078","DOI":"10.1002\/anbr.202000078","volume":"1","author":"Y Zhao","year":"2021","unstructured":"Zhao, Y., Li, Q., Chai, J. & Liu, Y. Cargo-templated crosslinked polymer nanocapsules and their biomedical applications. Adv. NanoBiomed Res. 1, 2000078 (2021).","journal-title":"Adv. NanoBiomed Res."},{"key":"1577_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45666-5","volume":"15","author":"R Pattipeiluhu","year":"2024","unstructured":"Pattipeiluhu, R. et al. Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection. Nat. Commun. 15, 1303 (2024).","journal-title":"Nat. Commun."},{"key":"1577_CR25","first-page":"24765","volume":"145","author":"H Yu","year":"2023","unstructured":"Yu, H. et al. Inverse cubic and hexagonal mesophase evolution within ionizable lipid nanoparticles correlates with mRNA transfection in macrophages. J. Am. Chem. Soc. 145, 24765\u201324774 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"1577_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27493-0","volume":"12","author":"X Han","year":"2021","unstructured":"Han, X. et al. An ionizable lipid toolbox for RNA delivery. Nat. Commun. 12, 7233 (2021).","journal-title":"Nat. Commun."},{"key":"1577_CR27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2310491120","volume":"120","author":"J Philipp","year":"2023","unstructured":"Philipp, J. et al. pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function. Proc. Natl Acad. Sci. USA 120, e2310491120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","volume":"15","author":"Q Cheng","year":"2020","unstructured":"Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR\u2013Cas gene editing. Nat. Nanotechnol. 15, 313\u2013320 (2020).","journal-title":"Nat. Nanotechnol."},{"key":"1577_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41596-022-00755-x","volume":"18","author":"X Wang","year":"2023","unstructured":"Wang, X. et al. Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery. Nat. Protoc. 18, 265\u2013291 (2023).","journal-title":"Nat. Protoc."},{"key":"1577_CR30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109256118","volume":"118","author":"SA Dilliard","year":"2021","unstructured":"Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR31","doi-asserted-by":"publisher","first-page":"17714","DOI":"10.1002\/anie.202106329","volume":"60","author":"DY Wang","year":"2021","unstructured":"Wang, D. Y. et al. Liposomes with water as a pH-responsive functionality for targeting of acidic tumor and infection sites. Angew. Chem. Int. Ed. Engl. 60, 17714\u201317719 (2021).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"1577_CR32","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.bpc.2005.04.012","volume":"117","author":"K Sagarik","year":"2005","unstructured":"Sagarik, K. & Chaiyapongs, S. Structures and stability of salt-bridge in aqueous solution. Biophys. Chem. 117, 119\u2013140 (2005).","journal-title":"Biophys. Chem."},{"key":"1577_CR33","doi-asserted-by":"publisher","first-page":"6405","DOI":"10.1021\/la9809372","volume":"15","author":"VM Gun\u2019ko","year":"1999","unstructured":"Gun\u2019ko, V. M. & Turov, V. V. Structure of hydrogen bonds and 1H NMR spectra of water at the interface of oxides. Langmuir 15, 6405\u20136415 (1999).","journal-title":"Langmuir"},{"key":"1577_CR34","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.actbio.2017.10.034","volume":"65","author":"H Ou","year":"2018","unstructured":"Ou, H. et al. Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells. Acta Biomater. 65, 339\u2013348 (2018).","journal-title":"Acta Biomater."},{"key":"1577_CR35","doi-asserted-by":"publisher","first-page":"12046","DOI":"10.1073\/pnas.1512465112","volume":"112","author":"P Zhang","year":"2015","unstructured":"Zhang, P. et al. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. Proc. Natl Acad. Sci. USA 112, 12046\u201312051 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207841119","volume":"119","author":"J Chen","year":"2022","unstructured":"Chen, J. et al. Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response. Proc. Natl Acad. Sci. USA 119, e2207841119 (2022).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR37","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.it.2012.02.007","volume":"33","author":"R F\u00f6rster","year":"2012","unstructured":"F\u00f6rster, R., Braun, A. & Worbs, T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol. 33, 271\u2013280 (2012).","journal-title":"Trends Immunol."},{"key":"1577_CR38","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41551-024-01285-5","volume":"9","author":"Y Zhao","year":"2025","unstructured":"Zhao, Y. et al. Antitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates. Nat. Biomed. Eng 9, 234\u2013248 (2025).","journal-title":"Nat. Biomed. Eng"},{"key":"1577_CR39","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1083\/jcb.105.6.2723","volume":"105","author":"DJ Yamashiro","year":"1987","unstructured":"Yamashiro, D. J. & Maxfield, F. R. Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells. J. Cell Biol. 105, 2723\u20132733 (1987).","journal-title":"J. Cell Biol."},{"key":"1577_CR40","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nchembio.1064","volume":"8","author":"M Schlame","year":"2012","unstructured":"Schlame, M. et al. The physical state of lipid substrates provides transacylation specificity for tafazzin. Nat. Chem. Biol. 8, 862\u2013869 (2012).","journal-title":"Nat. Chem. Biol."},{"key":"1577_CR41","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41563-020-00886-0","volume":"20","author":"S Liu","year":"2021","unstructured":"Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing. Nat. Mater. 20, 701\u2013710 (2021).","journal-title":"Nat. Mater."},{"key":"1577_CR42","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nbt.1602","volume":"28","author":"SC Semple","year":"2010","unstructured":"Semple, S. C. et al. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28, 172\u2013176 (2010).","journal-title":"Nat. Biotechnol."},{"key":"1577_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42280-9","volume":"14","author":"Y Zhao","year":"2023","unstructured":"Zhao, Y. et al. Nanomechanical action opens endo-lysosomal compartments. Nat. Commun. 14, 6645 (2023).","journal-title":"Nat. Commun."},{"key":"1577_CR44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2311276120","volume":"120","author":"C Wang","year":"2023","unstructured":"Wang, C., Zhao, C., Wang, W., Liu, X. & Deng, H. Biomimetic noncationic lipid nanoparticles for mRNA delivery. Proc. Natl Acad. Sci. USA 120, e2311276120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1577_CR45","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1038\/nm.2514","volume":"17","author":"M Phillipson","year":"2011","unstructured":"Phillipson, M. & Kubes, P. The neutrophil in vascular inflammation. Nat. Med. 17, 1381\u20131390 (2011).","journal-title":"Nat. Med."},{"key":"1577_CR46","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/ni.2921","volume":"15","author":"WM Nauseef","year":"2014","unstructured":"Nauseef, W. M. & Borregaard, N. Neutrophils at work. Nat. Immunol. 15, 602\u2013611 (2014).","journal-title":"Nat. Immunol."},{"key":"1577_CR47","doi-asserted-by":"publisher","first-page":"316","DOI":"10.3389\/fimmu.2014.00316","volume":"5","author":"C Vaure","year":"2014","unstructured":"Vaure, C. & Liu, Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front. Immunol. 5, 316 (2014).","journal-title":"Front. Immunol."},{"key":"1577_CR48","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1038\/s41551-024-01256-w","volume":"8","author":"N Chaudhary","year":"2024","unstructured":"Chaudhary, N. et al. Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d. Nat. Biomed. Eng. 8, 1483\u20131498 (2024).","journal-title":"Nat. Biomed. Eng."},{"key":"1577_CR49","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.it.2022.07.004","volume":"43","author":"D Capece","year":"2022","unstructured":"Capece, D. et al. NF-kappaB: blending metabolism, immunity, and inflammation. Trends Immunol. 43, 757\u2013775 (2022).","journal-title":"Trends Immunol."},{"key":"1577_CR50","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/s41563-018-0028-2","volume":"17","author":"AW Li","year":"2018","unstructured":"Li, A. W. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. 17, 528\u2013534 (2018).","journal-title":"Nat. Mater."}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01577-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01577-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01577-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:02:36Z","timestamp":1789509756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01577-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["1577"],"URL":"https:\/\/doi.org\/10.1038\/s41551-025-01577-4","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"25 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.J. and Y.Z. are authors of a US Provisional Application (No. 63\/723,698) related to this work filed on 22 November 2024 and S.J., Y.Z., Y.H. and P.L. an International (PCT) Application (No. PCT\/US2025\/056506) filed on 21 November 2025 by Cornell University. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}