Magnetite Nanoparticle Photothermal Therapy in a Pancreatic Tumor-on-Chip: A Dual-Action Approach Targeting Cancer Cells and their Microenvironment
Anastasiia Dubrova, Charles Cavaniol, Aurore Van de Walle, Paul Mathieu, Zoé Fusilier, Nader Yaacoub, Yoann Lalatonne, Stéphanie Descroix, Claire Wilhelm
Abstract
The application of magnetite nanoparticles (MagNPs) for photothermal therapy (MagNP-PTT) has recently expanded to cancer treatment. This study introduces MagNP-PTT in a tumor-on-a-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 1 week to form tumor spheroids. This platform offers a framework for applying PTT in a model system that aims 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 °C between 38-48 °C were established. Temperatures above 44 °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 an alternative approach for overcoming stromal barriers in pancreatic cancer treatment.