Bioengineered Chip Model for Magnetic-Nanoparticle-Driven Targeted Cancer Therapy

Magnetic drug targeting (MDT) leverages external magnetic fields to guide magnetic drug carriers (MDCs) to diseased sites. However, its clinical use is hindered by challenges such as the weakening of magnetic fields with tissue depth, MDC size/instability issues, and hydrodynamic shear. Despite years of research, progress remains limited due to the absence of reliable disease models, as animal models pose ethical and interspecies concerns, while current synthetic platforms struggle to replicate the tumor microenvironment (TME) and assess cellular responses to magnetic stimuli accurately. To address these limitations, we present an on-chip model developed using a lithography-free fabrication method to recreate physiologically relevant tumor conditions for evaluating MDC-assisted therapy. Our model closely replicates the breast TME by using an MDA-MB-231 cell-embedded hydrogel matrix flanked by two HUVEC-lined deformable microchannels, facilitating endothelial-tumor cell interactions and pressure-driven perfusion on-chip. As a proof of concept for targeted therapy applications, the platform was used to investigate MDT using a 10-20 nm (diameter) chitosan-coated MDC by assessing its retention against critical parameters such as variable magnetic fields and shear stress conditions, enabling precise magnetic-field calibration for optimal targeting. Subsequently, high-resolution imaging captured dose-response effects of the magnetically targeted drug via live/dead assays and immunocytochemistry studies, while flow cytometry and gene expression analysis revealed apoptotic pathway activation and reduced invasion markers. Overall, we establish our bioengineered chip as a cost-effective, scalable, and first-of-its-kind biomimetic system for MDT research designed to facilitate preclinical screening of potential anticancer therapies.