Theranostics 2020; 10(17):7921-7924. doi:10.7150/thno.49577


The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy

Yang Shi1✉, Roy van der Meel2✉, Xiaoyuan Chen3✉, Twan Lammers1,4,5✉

1. Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Aachen, Germany.
2. Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Maryland, USA.
4. Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands.
5. Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands.

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Shi Y, van der Meel R, Chen X, Lammers T. The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. Theranostics 2020; 10(17):7921-7924. doi:10.7150/thno.49577. Available from

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Following its discovery more than 30 years ago, the enhanced permeability and retention (EPR) effect has become the guiding principle for cancer nanomedicine development. Over the years, the tumor-targeted drug delivery field has made significant progress, as evidenced by the approval of several nanomedicinal anticancer drugs. Recently, however, the existence and the extent of the EPR effect - particularly in patients - have become the focus of intense debate. This is partially due to the disbalance between the huge number of preclinical cancer nanomedicine papers and relatively small number of cancer nanomedicine drug products reaching the market. To move the field forward, we have to improve our understanding of the EPR effect, of its cancer type-specific pathophysiology, of nanomedicine interactions with the heterogeneous tumor microenvironment, of nanomedicine behavior in the body, and of translational aspects that specifically complicate nanomedicinal drug development. In this virtual special issue, 24 research articles and reviews discussing different aspects of the EPR effect and cancer nanomedicine are collected, together providing a comprehensive and complete overview of the current state-of-the-art and future directions in tumor-targeted drug delivery.

Keywords: EPR effect, enhanced permeability and retention (EPR), cancer nanomedicine, tumor targeting, active targeting, cancer immunotherapy, extracellular vesicles, imaging