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

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°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 a novel approach for overcoming stromal barriers in pancreatic cancer treatment.