Editors' ChoiceNanomedicine

EPR or no EPR? The billion-dollar question

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Science Translational Medicine  01 Jul 2015:
Vol. 7, Issue 294, pp. 294ec112
DOI: 10.1126/scitranslmed.aac8108

The enhanced permeability and retention (EPR) effect describes the preferential accumulation of nanoparticles within tumors owing to their leaky vasculature and poor lymphatic drainage. First described almost 30 years ago, EPR has been a main reason behind the high enthusiasm for the development of nanoparticle therapeutics as cancer therapies. However, recent results from preclinical studies examining the EPR effect have been mixed, with some reports supporting preferential, EPR-mediated accumulation of nanomedicines within tumors, while others show that the EPR effect is highly dependent on the tumor model. Today, EPR remains a controversial topic in nanomedicine. To this end, Hansen et al. aimed to characterize the differences in EPR effect between different tumor histologies.

The authors used canine spontaneous tumors, which closely mimic the human condition, and 64Cu-labeled liposomes, which can be imaged by positron emission tomography. The biodistribution of these radiolabeled liposomes in 11 canine cancer patients revealed that, although most carcinomas had substantial liposome accumulation, most soft tissue sarcomas did not. Their data suggest that tumor histology may therefore have a significant effect on EPR. The investigators also suggest that such radiolabeled nanocarriers could be a useful tool in selecting patients that will benefit from nanoparticle therapeutics based on pretreatment biodistribution of nanoparticle imaging probes.

The results from this study are consistent with our understanding of human tumors. Fast-growing tumors such as carcinomas are very vascular and therefore have more porous/leaky blood vessels, whereas slow-growing tumors such as sarcomas are not extremely vascular. It is difficult to reach any firm conclusions for patients based on this study, owing to its small sample size and the fact that the results are from canine tumors. The results of this study will need to be validated in humans. Future research should investigate whether radiolabeled nanoparticles, such as the liposomes described by Hansen et al., can be used as biomarkers to better select patients that will benefit from nanoparticle therapeutics.

A. E. Hansen et al., Positron emission tomography based elucidation of the enhanced permeability and retention effect in dogs with cancer using copper-64 liposomes. ACS Nano 10.1021/acsnano.5b01324 (2015). [Abstract]

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