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In this study, we investigated how vesicle release rate, cellular proliferation, and tumour origin jointly shape EV\u2010associated protein output. Using a panel of 19 human, murine, canine and primate cancer\u2010 and non\u2010cancer cell lines cultured under standardized conditions, we isolated small extracellular vesicle\u2010enriched fractions and quantified particle number, EV\u2010associated protein content, cell number and proliferation rate and integrated these parameters into three complementary, readily computable metrics: protein content per particle (PP; pg\/particle), Vesicle Release Characteristics (VRC; particles\/cell\/24\u00a0h), and Protein Release Characteristics (PRC; pg\/cell\/24\u00a0h). Cancer cells showed significantly higher estimated EV release per cell than non\u2010cancer cells (\u223c3.6\u2010fold higher VRC), while their EV\u2010enriched isolates exhibited a substantially lower protein\u2010to\u2010particle ratio (\u223c4.3\u2010fold lower PP). Lower PP was independently associated with both cancer origin and proliferation rate and was not explained by differences in vesicle size. Despite the elevated vesicle output, cancer\u2010derived cells exported less total vesicular protein per cell and time unit (\u223c2.1\u2010fold lower PRC), and the relationship between vesicle output and total protein output itself differed between non\u2010cancer and cancer cells. These findings demonstrate that particle number and protein content describe distinct and non\u2010equivalent aspects of EV output. We therefore recommend integrated, multidimensional reporting (VRC, PRC, and the protein\/particle descriptor PP \u2014 or vesicles per pg protein) to enable biologically meaningful comparison and dosing of EV preparations.<\/jats:p>","DOI":"10.1002\/jex2.70188","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:55:16Z","timestamp":1789368916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When EV Dose Is Not What It Seems: Quantitative Mismatch Between Particle Number\u2010 and Protein\u2010Based Dosing"],"prefix":"10.1002","volume":"5","author":[{"given":"T\u00edmea","family":"B\u00f6r\u00f6czky","sequence":"first","affiliation":[{"name":"Institute of Biochemistry Biological Research Centre HUN\u2010REN  Szeged Hungary"},{"name":"Department of Immunology University of Szeged  Szeged Hungary"},{"name":"Doctoral School of Experimental and Preventive Medicine University of 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