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Here, we engineered a breast tumor\u2010on\u2010chip platform to investigate gold nanorod (AuNR)\u2010mediated PTT in a 3D type I collagen microenvironment using luminal\u2010like MCF7 and triple\u2010negative breast cancer MDA\u2010MB\u2010231 spheroids. A custom microfluidic architecture incorporating sliding\u2010wall technology enabled controlled lateral perfusion with a spatially restricted thermal response consistent with localized AuNR\u2010mediated heating within the central matrix compartment. Both tumor models exhibited pronounced cytotoxicity at temperatures above \u223c50\u00b0C and showed comparable half\u2010maximal responses in the Live\/Dead ratio dose\u2010response curves, corresponding to laser powers of approximately 0.48 and 0.38\u00a0W for MCF7 and MDA\u2010MB\u2010231 spheroids, respectively, despite their distinct epithelial and mesenchymal phenotypes. Immunofluorescence analyses 24\u00a0h after sublethal PTT revealed protein\u2010level changes, including an increased vimentin\u2010to\u2010E\u2010cadherin ratio and enhanced N\u2010cadherin expression, particularly in MCF7 spheroids. Complementary gene expression\u00a0analysis revealed treatment\u2010associated modulation of apoptosis\u2010, inflammation\u2010, and epithelial\u2010mesenchymal transition (EMT)\u2010associated genes, although most changes in EMT\u2010associated transcripts were modest and not statistically significant. Altogether, this work suggests treatment\u2010associated alterations in selected mesenchymal markers in MCF7 spheroids following sublethal photothermal stress, warranting further temporal and functional validation.<\/jats:p>","DOI":"10.1002\/smll.75343","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:39:56Z","timestamp":1787571596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Biomimetic Breast Tumor\u2010On\u2010Chip Platform Reveals Mesenchymal Marker Upregulation Following Gold Nanorod Photothermal Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-8948","authenticated-orcid":false,"given":"Camila A.","family":"Salvego","sequence":"first","affiliation":[{"name":"Centro de Lasers e Aplica\u00e7\u00f5es Instituto de Pesquisas Energ\u00e9ticas e Nucleares (IPEN\u2010CNEN) S\u00e3o Paulo Brazil"},{"name":"Laboratoire Physique des 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