{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:45:35Z","timestamp":1790567135947,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"50","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22261142665"],"award-info":[{"award-number":["22261142665"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Effective treatment of pulmonary diseases remains constrained by the scarcity of delivery systems capable of selective tissue targeting. Herein, we report a lung\u2010targeting platform created through the structural repurposing of hemoglobin (Hb). Acidic heating enables a conformational shift of Hb from \u03b1\u2010helix to \u03b2\u2010sheet, leading to its self\u2010assembly into fibrils (HbFs). Unexpectedly, intravenously injected HbFs exhibit rapid and specific accumulation in the lungs. Cryo\u2010electron microscopy (cryo\u2010EM) structure determination revealed a fibril surface rich in positively charged residues, which facilitates two key functions: selective binding to circulating platelets via a hitchhiking mechanism for lung targeting, and efficient electrostatic complexation with mRNA. In a therapeutic application, HbFs loaded with mRNA encoding an interleukin\u201011 single\u2010chain fragment variable (IL\u201011 scFv) were administered in a murine model of bleomycin\u2010induced pulmonary fibrosis. The formulation achieved lung\u2010specific delivery with predominant uptake by pulmonary fibroblasts, enabling sustained local IL\u201011 scFv expression. Consequently, treatment significantly suppressed fibroblast activation and migration, attenuated collagen deposition, restored lung function. This work establishes HbFs as a novel protein\u2011based vehicle for targeted mRNA delivery, leveraging natural cellular trafficking pathways to enable localized therapy for lung disorders.<\/jats:p>","DOI":"10.1002\/advs.76092","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T18:59:49Z","timestamp":1781290789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hemoglobin's \u03b1\u2010Helix\u2010to\u2010\u03b2\u2010Sheet Transition Enables Targeted mRNA Delivery to the Lung"],"prefix":"10.1002","volume":"13","author":[{"given":"Xihua","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3177-1364","authenticated-orcid":false,"given":"Saiya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangjian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long Shuang","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiguo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2031-9513","authenticated-orcid":false,"given":"Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Cao","sequence":"additional","affiliation":[{"name":"Bio\u2010X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yapeng","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"},{"name":"School of Health Science &amp; Engineering University of Shanghai for Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-7648","authenticated-orcid":false,"given":"Yiping","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Engineering School of Agriculture &amp; Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.06.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.243"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010021\u201000358\u20100"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-025-01124-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010023\u201001086\u2010x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c10648"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010025\u201002381\u2010w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222\u2010025\u201000321\u20106"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000825\u2010x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010022\u201001071\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2025.101436"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202517893"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2502796"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(24)01804\u2010X"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)01044\u2010X"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnad037"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2017.58"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43016\u2010025\u201001260\u20106"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.11.020"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509821"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-65976-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.008"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201048838\u20105"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/nl3004896"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq2072"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21706"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039598\u20109"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115645"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1292"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062688"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100613200"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005079\u20107"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010bioeng\u2010121219\u2010024239"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010020\u201000886\u20100"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042280\u20109"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw1237"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010med\u2010041818\u2010011649"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010020\u201000531\u20105"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051056\u20108"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119590"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm809"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.73"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn7162"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010020\u20100669\u20106"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050093\u20107"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042948\u20102"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76092","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76092","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T07:38:56Z","timestamp":1788766736000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":46,"journal-issue":{"issue":"50","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.76092"],"URL":"https:\/\/doi.org\/10.1002\/advs.76092","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"2026-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76092"}}