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Human solid tumors and clinical relevance of the enhanced permeation and retention effect: a ‘golden gate’ for nanomedicine in preclinical studies?

    Poonam Gawali

    Cancer Research Institute, Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi-Mumbai-410210, MH, India

    ,
    Aishwarya Saraswat

    College of Pharmacy & Health Sciences, St. John's University, Queens, New York, NY 11439, USA

    ,
    Shruti Bhide

    Cancer Research Institute, Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi-Mumbai-410210, MH, India

    ,
    Sanjay Gupta

    The Department of Pharmacology & Therapeutics, Seth Gordhandas Sunderdas Medical College & the King Edward Memorial Hospital, Parel, Mumbai, 400012, India

    Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, MH, India

    &
    Ketan Patel

    *Author for correspondence: Tel.: +1 718 990 6828;

    E-mail Address: patelk2@stjohns.edu

    College of Pharmacy & Health Sciences, St. John's University, Queens, New York, NY 11439, USA

    Published Online:https://doi.org/10.2217/nnm-2022-0257

    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

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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