Modelling cargo loaded macrophage trafficking across liver endothelium: a new approach to drug delivery in liver cancer

Cases of primary liver cancer, also known as hepatocellular cancer (HCC) are rising rapidly in the UK and new therapies are urgently needed. Immune therapy has shown promising results and in this project we want to explore the potential of using a specific immune cell called macrophages. Pre-cursor macrophages, called monocytes, are found in our blood circulation but they can leave the circulation and enter organs throughout the body. Macrophages are attractive as a target for immunotherapy as their behavior can be altered to attack tumours and they can also potentially acts as drug delivery agents because they can engulf particles and transport them to sites of disease. To help their delivery we are studying how macrophages can cross blood vessels through cells called endothelial cells. We will use cutting edge imaging and modelling to see how macrophages cross the liver endothelial cells in different physical environments of fluid flow and endothelial stiffness and assess how efficient this process is when macrophages are pre-loaded with cargo. This project will help understand the physical factors which control macrophages crossing the liver barrier and help to design new approaches to promote macrophage cell therapy for liver cancer.