Advocation and advancements of EPR effect theory in drug delivery science: A commentary

To honor the contributions of Professor Hiroshi Maeda to the progress of targeted drug delivery research, a brief review of enhanced permeability and retention (EPR) effect theory proposed by him as the physiology-based principal mechanism of intra-tumoral accumulation of large molecules and small particles is presented. Under historical and practical backgrounds in developments of various drug delivery systems including macromolecular conjugates, the concept of EPR effect was advocated in mid1980s and has cultivated new cancer chemotherapeutic modalities until recently. Namely, nanoplatforms such as polymer conjugates, liposomes, polymeric micelles, and nanoparticles have been studied as a promising fusion area for nanotechnology and medicine. Modulation of EPR effect by chemical and/or mechanical approaches to achieve tumor vascular and tissue modification would further lead to sophistication of cancer chemotherapy employing nanomedicines.