Strategies to improve the EPR effect for the delivery of anti-cancer nanomedicines

The enhanced permeability and retention effect of nanoparticles has become the gold standard principle for cancer drug delivery systems, holding the promise of safe, simple and effective therapy. Nevertheless, due to its poor clinical translation, many recent papers describe the limitations of this EPR effect. Hence, efforts should be provided to overcome these barriers allowing the enhancement of nanomedicines on the market. This communication reviews three main strategies to enhance the EPR effect: (i) the normalization of the tumor vasculature; (ii) the possibility to include collagenase or hyaluronidase into the tumor microenvironment to simultaneously improve the transport and reduce the interstitial fluid pressure and (iii) the increase of the tumor permeability using external or internal stimuli.