{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:00:17Z","timestamp":1790697617681,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In vivo immune modulation can potentially benefit broader cancer patients. Efficient cross\u2010priming of anti\u2010tumor T cells requires \u201cthree\u2010signal\u201d dendritic cells (DCs) that simultaneously integrate antigenic, co\u2010stimulatory, and migratory programs, which remains a major challenge. Here, we developed a carrier\u2010free peptide\u2013cyclic dinucleotide (CDN) nanoconjugate (PCN) that co\u2010activates immunogenic cell death (ICD) in tumors and stimulator of interferon genes (STING) signaling in DCs. Library screening identified ICD\u2010inducing peptides enriched in hydrophobic and cationic residues that promote self\u2010assembly, cell penetration, and ICD potency. Mechanistic studies revealed peptides can trigger overlapping pyroptosis, necroptosis, and apoptosis, with lysosomal damage and cathepsin release as dominant upstream drivers. PCN promoted tumor\u2010antigen release and facilitated cytosolic CDN delivery for robust STING activation. This dual functionality induced early cytokine and chemokine responses and generated cDC1\u2010enriched \u201cthree\u2010signal\u201d migratory DCs trafficking from tumors to draining lymph nodes, resulting in enhanced antigen\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell activation and memory formation. PCN also broadly reprogrammed the tumor microenvironment toward anti\u2010tumor immunity. In preclinical models, PCN induced complete tumor rejection in 70% of B16\u2010F10\u2010 or CT26\u2010bearing mice and provided durable protection against tumor rechallenge when combined with\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010PD\u20101.\n                  <\/jats:p>","DOI":"10.1002\/adma.74918","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:01:45Z","timestamp":1790694105000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanoconjugate Strategy Integrating Immunogenic Cell Death Induction and Innate Immune Activation for Potent Anti\u2010Cancer Immunity"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-4849","authenticated-orcid":false,"given":"Tengyu","family":"He","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Cryer","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6341-9089","authenticated-orcid":false,"given":"Daniela","family":"Simental Lopez","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-9345","authenticated-orcid":false,"given":"Zhenyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-0183","authenticated-orcid":false,"given":"Erin M.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4481-4287","authenticated-orcid":false,"given":"Yongkuk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vargas Franyuti","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-9780","authenticated-orcid":false,"given":"Eliz","family":"Amar\u2010Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-6069","authenticated-orcid":false,"given":"Natalie","family":"Artzi","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University  Boston Massachusetts USA"},{"name":"Institute for Medical Engineering and Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010025\u201001015\u2010z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi6899"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.10.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02864"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000823\u2010w"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000789\u20104"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102497"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089263"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.06.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3709"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201044787\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013368\u2010y"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010021\u201000459\u20107"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.11"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6b03329"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008510\u2010w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010018\u20100236\u20108"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010020\u20100288\u20103"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010022\u201001225\u2010x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010023\u201001447\u20107"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010022\u201001251\u2010z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222\u2010025\u201000337\u2010y"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20101059"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000339\u2010z"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010025\u201000934\u20101"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010025\u201000927\u20100"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010024\u201000681\u2010y"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201002024\u20103"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010024\u201001245\u20108"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011269\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1167105"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010025\u201001018\u2010w"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202307679"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2570293.x"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010025\u201002164\u20103"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.107"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010023\u201000749\u20108"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010024\u201000920\u20109"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10400"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010020\u201000630\u20103"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201003032\u20105"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200508"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417\u2010024\u201000765\u20109"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010021\u201000670\u20103"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201027692\u20109"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13253"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010018\u20100469\u20101"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.037"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.003"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303380"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)80434\u20101"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2153"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014479"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478\u2010811X\u20108\u201031"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400851"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000436722.46675.4a"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/zaac.200800297"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010023\u201001630\u20100"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010021\u201000547\u20106"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010022\u201000589\u20106"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201100108"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74918","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.74918","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:01:47Z","timestamp":1790694107000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.74918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":69,"alternative-id":["10.1002\/adma.74918"],"URL":"https:\/\/doi.org\/10.1002\/adma.74918","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e74918"}}