Brain metastases, frequently associated with primary lung cancer, are among the most challenging complications of advanced cancer, largely because the blood-brain barrier (BBB) severely restricts the delivery of therapeutic agents to the brain. This project aims to develop plant virus-derived virus-like particles (VLPs) as multifunctional nanoshuttles for targeted drug delivery to brain metastatic tumors. Brome Mosaic Virus (BMV)-derived VLPs will provide a distinctive and versatile platform for encapsulating antitumor drugs and functionalizing their surface with targeting molecules to promote BBB crossing and tumor targeting. The therapeutic performance of the multifunctionalized VLPs will be investigated using advanced interconnected Brain-on-Chip and Lung-on-Chip microfluidic models that will reproduce key features of the human brain and lung microenvironments, respectively, and relevant aspects of the lung-to-brain metastatic pathway. These models will enable the dynamic evaluation of VLP transport and therapeutic responses under flow conditions. By combining plant-derived VLP nanotechnology with Organ-on-Chip models, this project seeks to advance targeted nanomedicine for brain metastases and provide new insights into BBB transport, tumor targeting, and therapeutic efficacy.