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Fucoidan, a sulphated polysaccharide, has demonstrated anticancer activity with an undefined mechanism. Here, we investigated the biological effects of fucoidan (FU) and fucoidan nanoaggregates (NFU) in both thyroid cancer (SW1736) and non-tumorigenic thyroid cells (Nthy-ori 3.1). NFU showed a mean diameter of ~\u2009187\u00a0nm, a low polydispersity (~\u20090.2) and a negative Zeta potential. NFU significantly reduced SW1736 cell viability, reaching\u2009~\u200960% inhibition at 0.01\u00a0mg\/mL and ~\u200980% at 0.1\u00a0mg\/mL after 72\u00a0h, while sparing non-tumorigenic cells. Mechanistically, NFU induced marked lysosomal enlargement selectively in tumor cells and localized predominantly within LAMP-1\u2013positive compartments. Consistently, tumor cells showed constitutive Cathepsin D maturation and enhanced sensitivity to NFU-induced lysosomal perturbation. Collectively, these findings identify lysosomes as a primary intracellular target of fucoidan-based nanosystems and reveal a tumor-selective vulnerability to NFU-mediated lysosomal stress. This study provides the first quantitative evidence of lysosomal targeting by fucoidan nanoparticles in thyroid cancer cells and supports NFU as a promising lysosome-directed nanotherapeutic strategy for aggressive thyroid malignancies.<\/jats:p>","DOI":"10.1038\/s41598-026-52121-6","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:15:36Z","timestamp":1778562936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lysosomal vulnerability as a therapeutic target in thyroid cancer using fucoidan nanoparticles"],"prefix":"10.1038","volume":"16","author":[{"given":"Marilena","family":"Celano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Gagliardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Giuliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Cosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Fiume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"52121_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1530\/ETJ-24-0287","volume":"14","author":"N Kiyota","year":"2025","unstructured":"Kiyota, N., Koyama, T. & Sugitani, I. 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