{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T10:43:22Z","timestamp":1786272202976,"version":"build-2736575974"},"posted":{"date-parts":[[2026,3,2]]},"group-title":"Bioengineering","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35GM150507"],"award-info":[{"award-number":["R35GM150507"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35GM146786"],"award-info":[{"award-number":["R35GM146786"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21HL168650"],"award-info":[{"award-number":["R21HL168650"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21CA291723"],"award-info":[{"award-number":["R21CA291723"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2003789"],"award-info":[{"award-number":["2003789"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"award":["25-18467S"],"award-info":[{"award-number":["25-18467S"]}],"id":[{"id":"https:\/\/ror.org\/01pv73b02","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Union REFRESH-Research Excellence for Region Sustainability and High-tech Industries project","award":["CZ.10.03.01\/00\/22_003\/0000048"],"award-info":[{"award-number":["CZ.10.03.01\/00\/22_003\/0000048"]}]},{"name":"ERDF\/ESF project TECHSCALE","award":["CZ.02.01.01\/00\/22_008\/0004587"],"award-info":[{"award-number":["CZ.02.01.01\/00\/22_008\/0004587"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Premature clearance and limited organ targeting remain major barriers for nanoparticle (NP) drug delivery. Hitchhiking NPs on red blood cells (RBCs) can enhance circulation and organ-selective accumulation, but most approaches require\n                  <jats:italic>ex vivo<\/jats:italic>\n                  RBC extraction and reinfusion, limiting clinical translation. Here, we report an\n                  <jats:italic>in situ<\/jats:italic>\n                  RBC-hitchhiking strategy, named i-Bind, which employs polyphenol surface functionalization to enable spontaneous NP attachment to RBCs directly in the bloodstream. Driven by strong interactions of phenolic motifs with RBC membranes, i-Bind NPs exhibited markedly enhanced and more stable hitchhiking onto RBCs under flowing whole blood conditions. In both healthy and diseased mice, i-Bind NPs preferentially target the lungs, resulting in an over 20-fold increase in lung-to-liver deposition ratio compared to unmodified NPs. Additionally, i-Bind NPs show preferential targeting to distinct lung immune cell subsets in a pathology-dependent manner, including cDC2s in healthy lungs, neutrophils in acute lung injury, and cDC1s in lung metastases. In a melanoma lung metastasis model, delivery of the STING agonist diABZI via i-Bind NPs significantly inhibited lung metastasis progression by reprogramming the lung immune microenvironment. Collectively, i-Bind provides a simple and versatile platform for organ-targeted drug delivery and immune reprogramming.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Teaser<\/jats:title>\n                  <jats:p>\n                    Surface functionalization of nanoparticles enables\n                    <jats:italic>in situ<\/jats:italic>\n                    red blood cell hitchhiking, unlocking new paths for organ-selective immune reprogramming\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.27.708550","type":"posted-content","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:35:19Z","timestamp":1772519719000},"source":"Crossref","is-referenced-by-count":0,"title":["Lung-Selective Immune Reprogramming via\n                  <i>In Situ<\/i>\n                  Red Blood Cell Hitchhiking Nanoparticles"],"prefix":"10.64898","author":[{"given":"Edidiong M.","family":"Udofa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Moein","family":"Naderi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirushi","family":"Gunasekara","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Jia","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeonghun","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"\u010cechov\u00e1","sequence":"additional","affiliation":[{"name":"Regional Center of Advanced Technologies and Materials, The Czech Advanced Technology and Research Institute (CATRIN), Palack\u00fd University Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00e9ta","family":"Palonc\u00fdov\u00e1","sequence":"additional","affiliation":[{"name":"Regional Center of Advanced Technologies and Materials, The Czech Advanced Technology and Research Institute (CATRIN), Palack\u00fd University Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan S.","family":"Nikolic","sequence":"additional","affiliation":[{"name":"UICentre for Drug Discovery, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Herrera-Alonso","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering, Colorado State University, Fort Collins, Colorado, USA"},{"name":"School of Biomedical and Chemical Engineering, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying S.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois Chicago, Chicago, Illinois, USA"},{"name":"Department of 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