{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:04:20Z","timestamp":1789452260136,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/03635-8 , 23\/09650-0"],"award-info":[{"award-number":["2017\/03635-8 , 23\/09650-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["140227\/2021-0"],"award-info":[{"award-number":["140227\/2021-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006417","name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o, Universidade Estadual de Campinas","doi-asserted-by":"publisher","award":["519.287"],"award-info":[{"award-number":["519.287"]}],"id":[{"id":"10.13039\/501100006417","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Extracellular vesicles (EVs) have been investigated as promising vehicles for delivering drugs and microRNAs (miRNAs) in distinct types of cancer. However, their use as a delivery system in papillary thyroid carcinoma (PTC) remains underexplored. PTC is the most prevalent subtype of thyroid cancer, and despite its good prognosis, a fraction of the cases evolve into aggressive and fatal forms. Here, we investigated whether non-tumor thyroid cells can be engineered to produce EVs-enriched with tumor suppressor miRNAs that could be delivered to PTC cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      EVs from NThy-ORI cells transfected with\n                      <jats:italic>miR-485-5p<\/jats:italic>\n                      or\n                      <jats:italic>miR-495-3p<\/jats:italic>\n                      were isolated by differential ultracentrifugation and characterized by Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western Blot. Functional\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays were conducted to explore the impact of miRNA-enriched EVs on PTC progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Non-tumor thyroid NThy-ORI cells overexpressing\n                      <jats:italic>miR-485-5p<\/jats:italic>\n                      or\n                      <jats:italic>miR-495-3p<\/jats:italic>\n                      efficiently produced EVs enriched with these miRNAs, which were internalized by PTC cells. Treatment with miRNA-enriched EVs modulated the expression of validated miRNA targets and key epithelial\u2013mesenchymal transition-related genes, leading to a 40% reduction in migration (p&amp;lt;0.0001) and a 60% reduction in invasion in both miRNAs and cell lines tested (p&amp;lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest the potential of thyroid-derived EVs as a biologically relevant and promising system for delivering tumor suppressor miRNAs, opening new opportunities to explore this approach as a therapeutic strategy for PTC.<\/jats:p>\n                  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