Human Solid Tumors and Clinical Relevance of The Enhanced Permeation and Retention Effect: A ‘Golden Gate’ for Nanomedicine in Preclinical Studies?

Abstract

Nanocarriers passively accumulate in solid tumors through irregular wide fenestrations in neovasculature and increased retention due to poor lymphatic drainage, a phenomenon termed the enhanced permeation and retention (EPR) effect. Although several preclinical reports have described the role of EPR in nanomedicine, its role in human solid tumor is obscure. There are several distinct factors for tumors in mice versus humans, including size, heterogeneity and nanomedicine pharmacokinetics. This review focuses on preclinical and clinical studies demonstrating the role of the EPR effect and passive targeting. The article illustrates the gaps that limit clinical effectiveness of the EPR effect and elaborates strategies to boost its efficiency, relaying future clinical outcomes for designing clinically applicable EPR-based nanomedicine.

Plain language summary

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.

Tweetable abstract

The gap between preclinical and clinical studies pertaining the EPR effect and strategies to boost its efficiency are elaborated to offer future directions for designing clinically applicable EPR-based anticancer nanomedicine. #EPR #EPREffect #Preclinical #Clinical #Cancer #Nanomedicine #PassiveTargeting

Graphical abstract

Keywords::

• EPR effect
• nanomedicine
• preclinical studies
• solid tumor
• tumor microenvironment
• tumor targeting

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Editorial board disclosure

K Patel is a member of the Nanomedicine Editorial Board. K Patel was not involved in any editorial decisions related to the publication of this article, and all author details were blinded to the article’s peer reviewers as per the journal’s double-blind peer review policy.

Acknowledgments

The authors thank B Khade (University of Mumbai) for providing Biorender software.

Additional information

Funding

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.