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bioRxiv · 10.1101/2025.02.06.636875

Magnetite Nanoparticle Photothermal Therapy in a Pancreatic Tumor-on-Chip: A Dual-Action Approach Targeting Cancer Cells and their Microenvironment

Dubrova, A.·Cavaniol, C.·Van de Walle, A.·Mathieu, P.·Fusilier, Z.·Yaacoub, N.·Lalatonne, Y.·Descroix, S.·Wilhelm, C.
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Abstract

The application of magnetite nanoparticles (MagNPs) for photothermal therapy (MagNP-PTT) has recently expanded in cancer treatment. This study introduces MagNP-PTT in a tumor-on-chip model to target highly aggressive pancreatic ductal adenocarcinoma (PDAC). A tumor-on-chip system was developed using PANC-1 PDAC cells embedded in a collagen type I extracellular matrix and cultured for one week to form tumor spheroids. This platform serves as the foundation for applying PTT in a model system that is aimed to mimic the native tumor microenvironment. MagNPs efficiently penetrate the tumor spheroids, achieving controlled heating via near-infrared (NIR) light. By adjusting nanoparticle concentration and laser power, temperature increments of 2{degrees}C between 38-48{degrees}C were established. Temperatures above 44{degrees}C significantly increased cell death, while lower temperatures allowed partial recovery. Beyond inducing cancer cell death, MagNP-PTT altered the extracellular matrix, and triggered a slight epithelial-mesenchymal transition marked by increased vimentin expression. These findings highlight MagNP-PTT as a dual-action therapy, targeting both tumor cells and their microenvironment, offering a novel approach for overcoming stromal barriers in pancreatic cancer treatment. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/636875v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@9b9c20org.highwire.dtl.DTLVardef@272c7aorg.highwire.dtl.DTLVardef@1d91021org.highwire.dtl.DTLVardef@1b1ea8d_HPS_FORMAT_FIGEXP M_FIG SYNOPSIS TABLE OF CONTENTS C_FIG

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Dubrova, A., Cavaniol, C., Van de Walle, A., Mathieu, P., Fusilier, Z., Yaacoub, N., Lalatonne, Y., Descroix, S., Wilhelm, C.. 2025-02-08. Magnetite Nanoparticle Photothermal Therapy in a Pancreatic Tumor-on-Chip: A Dual-Action Approach Targeting Cancer Cells and their Microenvironment. https://doi.org/10.1101/2025.02.06.636875

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