{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:32:00Z","timestamp":1789471920797,"version":"build-2803163510"},"reference-count":31,"publisher":"IOP Publishing","issue":"2","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":10,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81870542"],"award-info":[{"award-number":["81870542"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Mater."],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dendritic cells (DCs) are the most potent antigen-presenting cells with multifaceted functions in controlling immune activation and tolerance. Graves\u2019 disease, particularly Graves\u2019 ophthalmopathy, is recognized as a refractory autoimmune thyroid disease. Therefore, DC-targeted therapies aimed at inducing specific immune tolerance are important for the treatment of Graves\u2019 disease. Therefore, we utilized polylactic acid glycolic acid polymer (PLGA) polymer nanoparticles (NPs) encapsulating Graves\u2019 disease auto-antigen thyrotropin receptor A (TSHR-A) peptide and the immune tolerance inducer rapamycin (Rapa) to synthesize drug-loaded NPs (NP (TSHR-A + Rapa)). We first characterized the synthesized nanodrugs using transmission electron microscopy and dynamic light scattering techniques and tested the uptake capacity of DCs for NPs after co-culturing the NPs with DCs. And the safe concentration of NPs to DCs was detected using Cell counting kit-8 (CCK-8) assay. Subsequently, we tested the targeting and safety of the NPs in mice. And the effects of NPs on the proportion and proliferation of DCs and regulatory T (Treg) cells were examined <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> using flow cytometry and 5-ethynyl-2\u2032-deoxyuridine (EdU) method, respectively. Enzyme linked immunosorbent assay (ELISA) assays were used to detect the effect of NPs on cytokine release from DCs. Finally, we tested the preventive and therapeutic effects of the synthesized NPs on disease models. Our results showed that the synthesized NPs were well taken up by DCs <jats:italic>in vitro<\/jats:italic>, while <jats:italic>in vivo<\/jats:italic> they were mainly targeted to the spleen of mice. The NPs were able to relatively inhibit the maturation of DCs <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, while affecting the release of relevant cellular functional factors from DCs, and the NPs also promoted the proportion and proliferation of Treg cells <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. In addition, the synthesized NPs were able to prevent and improve the mouse disease model well without toxic side effects on mouse organs and other physiological indicators. Therefore, the synthesis of NP (TSHR-A + Rapa) NPs using PLGA encapsulated TSHR-A and rapamycin could be used as targeting DCs to alter immune tolerance and as a new potential approach for the treatment of Graves\u2019 disease.<\/jats:p>","DOI":"10.1088\/1748-605x\/adbaa3","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T22:53:56Z","timestamp":1740610436000},"page":"025045","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["PLGA nanoparticles encapsulating TSHR-A and rapamycin enhance the induction of dendritic cell-specific immune tolerance in mice with Graves\u2019 disease"],"prefix":"10.1088","volume":"20","author":[{"given":"Kun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-0900","authenticated-orcid":true,"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"bmmadbaa3bib1","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Disease","volume":"375","author":"Smith","year":"2016","journal-title":"N. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2024-05-14","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-02-26","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-03-11","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}