Figure 2. Biological barriers contributing to heterogeneity in EPR-mediated tumor targeting.

Multiple different vascular and microenvironmental parameters contribute to heterogeneity in EPR-based nanomedicine accumulation. At the vessel level, these include vascular permeability, endothelial cell receptor expression and vascular maturation. Stromal parameters which contribute to heterogeneity in EPR-based nano-tumor targeting are the extracellular matrix, tumor cell density, hypoxia and the interstitial fluid pressure. All of these pathophysiological parameters have to be considered when aiming to developed individualized and improved nanomedicine treatments.