A Biomimetic Breast Tumor‐On‐Chip Platform Reveals Mesenchymal Marker Upregulation Following Gold Nanorod Photothermal Therapy

Vollständiger Abstract

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ABSTRACT Photothermal therapy (PTT) using plasmonic nanoparticles has emerged as a promising strategy for localized cancer treatment, yet physiologically relevant models for assessing cell‐line model‐dependent responses remain limited. Here, we engineered a breast tumor‐on‐chip platform to investigate gold nanorod (AuNR)‐mediated PTT in a 3D type I collagen microenvironment using luminal‐like MCF7 and triple‐negative breast cancer MDA‐MB‐231 spheroids. A custom microfluidic architecture incorporating sliding‐wall technology enabled controlled lateral perfusion with a spatially restricted thermal response consistent with localized AuNR‐mediated heating within the central matrix compartment. Both tumor models exhibited pronounced cytotoxicity at temperatures above ∼50°C and showed comparable half‐maximal responses in the Live/Dead ratio dose‐response curves, corresponding to laser powers of approximately 0.48 and 0.38 W for MCF7 and MDA‐MB‐231 spheroids, respectively, despite their distinct epithelial and mesenchymal phenotypes. Immunofluorescence analyses 24 h after sublethal PTT revealed protein‐level changes, including an increased vimentin‐to‐E‐cadherin ratio and enhanced N‐cadherin expression, particularly in MCF7 spheroids. Complementary gene expression analysis revealed treatment‐associated modulation of apoptosis‐, inflammation‐, and epithelial‐mesenchymal transition (EMT)‐associated genes, although most changes in EMT‐associated transcripts were modest and not statistically significant. Altogether, this work suggests treatment‐associated alterations in selected mesenchymal markers in MCF7 spheroids following sublethal photothermal stress, warranting further temporal and functional validation.