Human solid tumors and clinical relevance of the enhanced permeation and retention effect: a 'golden gate' for nanomedicine in preclinical studies?

Unlike healthy organ vasculature in organs, solid tumor vasculature is leaky with poor lymphatic drainage. Nanoparticles <200 nm are reported to be selectively taken up in the tumor due to this tumor physiology, a process referred to as the enhanced permeation and retention (EPR) effect. Despite lots of preclinical evidence, there is lack of clinical success observed for EPR effect in human tumors. There are several factors responsible for this poor preclinical to clinical rendition of nanomedicine delivery to tumors by EPR effect. We have highlighted key differences between murine and human tumor models as well as listed effective approaches to boost the EPR effect in nanomedicine. These strategies will bridge the gaps that limit clinical translation of EPR-based nanomedicine and lay the groundwork to design effective anticancer therapies.