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This study examines a biophysical strategy that employs shear\u2010responsive RBC (sr\u2010RBC) carriers to mechanically release drugs at stenotic arteries. Intracellularly loaded sr\u2010RBCs exhibited shear\u2010dependent cargo release when perfused through stenotic arterial models, while no release was observed in unconstricted vessels. Notably, the sheared sr\u2010RBCs retained their membrane integrity and CD47 expression while maintaining their ability to traverse microvascular networks without release when perfused through a microfluidic model simulating pulmonary capillaries. Multiscale modelling of RBC suspension fluid dynamics demonstrates a strong positive correlation between the sr\u2010RBC drug release and the overall RBC membrane stretching induced by the high shear rates at various stenotic percentages. Sr\u2010RBCs and mechanosensitive cell carriers may enable new avenues for treating life\u2010threatening arterial constrictions and other vascular diseases.<\/jats:p>","DOI":"10.1002\/smll.74818","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:13:52Z","timestamp":1785492832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Shear\u2010Responsive Red Blood Cell Carriers for Targeted Drug Delivery to Constricted Arteries"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7914-7932","authenticated-orcid":false,"given":"Danielle Nemcovsky","family":"Amar","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4912-8103","authenticated-orcid":false,"given":"Rukiye","family":"Tuna","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomedical Engineering FAMU\u2010FSU College of Engineering  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7921-7064","authenticated-orcid":false,"given":"Tirosh","family":"Mekler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merav","family":"Belenkovich","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Korneyev","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5713-9981","authenticated-orcid":false,"given":"Yevgeniy","family":"Kreinin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Glozman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-3842","authenticated-orcid":false,"given":"Josu\u00e9","family":"Sznitman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Technion Israel Institute of Technology Technion City  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-6520","authenticated-orcid":false,"given":"Donald E.","family":"Ingber","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Vascular Biology Program Department of Surgery Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Harvard John A. 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