{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:06:31Z","timestamp":1785423991455,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ablink Biotech Co., Ltd."},{"name":"Sichuan Science and Technology Program","award":["2025YFMS0003"],"award-info":[{"award-number":["2025YFMS0003"]}]},{"DOI":"10.13039\/501100013792","name":"Chengdu University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013792","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/034z67559","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background: The mucosal barrier presents a significant challenge for non-invasive delivery of macromolecular therapeutics, often requiring administration with poor bioavailability and increased toxicity risks. The polymeric immunoglobulin receptor (pIgR) contains an extracellular secretory component (SC) for immunoglobulin binding and a membrane-anchored stem domain capable of apical-to-basolateral transcytosis. We hypothesized that targeting the stem domain could enable active drug transport across mucosal barriers. Methods: Using phage display, we identified four high-affinity nanobodies against human and murine pIgR. Two lead candidates (3LTHMP-4 and 3LTHMP-5) demonstrated efficient apical-to-basolateral transport in vitro (Transwell assays) and in vivo (fluorescence imaging). Engineered bispecific antibodies fusing these nanobodies with anti-IL-5 mAb reslizumab were administered via inhalation in a murine asthma model at one-tenth the intraperitoneal reslizumab dose. Resluts: The bispecific antibodies showed significant therapeutic efficacy, while reslizumab alone at equivalent concentrations failed to demonstrate efficacy. Hydrogen\u2013Deuterium Exchange Mass Spectrometry (HDX-MS) revealed that both 3LTHMP-4 and 3LTHMP-5 specifically bind to the pIgR stem domain (residues 578\u2013612), a region distinct from the dimeric IgA binding site. Conclusions: These findings suggest that stem domain-specific binding may facilitate transport across the mucosal barrier while preserving native receptor physiology, offering a potential strategy for effective transmucosal delivery of biologics.<\/jats:p>","DOI":"10.3390\/antib15040053","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pIgR Stem Zone-Targeted Nanobodies as Apical-to-Basolateral Carriers for Inhaled Biologic Delivery Across Mucosal Barriers"],"prefix":"10.3390","volume":"15","author":[{"given":"Aidong","family":"Qiu","sequence":"first","affiliation":[{"name":"College of Food and Bioengineering, Chengdu University, Chengdu 610106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Chengdu University, Chengdu 610106, China"},{"name":"Ablink Biotech, Chengdu 610200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyingjie","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Chengdu University, Chengdu 610106, China"},{"name":"Ablink Biotech, Chengdu 610200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ablink Biotech, Chengdu 610200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"He","sequence":"additional","affiliation":[{"name":"Ablink Biotech, Chengdu 610200, China"},{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Chengdu University, Chengdu 610106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3452-4510","authenticated-orcid":false,"given":"Jianghai","family":"Liu","sequence":"additional","affiliation":[{"name":"Ablink Biotech, Chengdu 610200, China"},{"name":"School of Bioscience and Technology, Chengdu Medical College, Chengdu 610500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1242\/jcs.193482","article-title":"The mucosal barrier at a glance","volume":"130","author":"France","year":"2017","journal-title":"J. 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