Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 860-8556, Japan.
Adv Drug Deliv Rev. 2020;157:142-160. doi: 10.1016/j.addr.2020.06.005. Epub 2020 Jun 14.
The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors that is related to their particular anatomical and pathophysiological characteristics, e.g. defective vascular architecture; large gaps between endothelial cells in blood vessels; abundant vascular mediators such as bradykinin, nitric oxide, carbon monoxide, and vascular endothelial growth factor; and impaired lymphatic recovery. These features lead to tumor tissues showing considerable extravasation of plasma components and nanomedicines. These data comprise the basic theory underlying the development of macromolecular agents or nanomedicines. The EPR effect is not necessarily valid for all solid tumors, because tumor blood flow and vascular permeability vary greatly. Tumor blood flow is frequently obstructed as tumor size increases, as often seen clinically; early stage, small tumors show a more uniform EPR effect, whereas advanced large tumor show heterogeneity in EPR effect. Accordingly, it would be very important to apply enhancers of EPR effect in clinical setting to make EPR effect more uniform. In this review, we discuss the EPR effect: its history, factors involved, and dynamics and heterogeneity. Strategies to overcome the EPR effect's heterogeneity may guarantee better therapeutic outcomes of drug delivery to advanced cancers.
增强的通透性和保留（EPR）效应是实体瘤的一种独特现象，与它们特定的解剖和病理生理学特征有关，例如血管结构缺陷；血管内皮细胞之间的大间隙；丰富的血管介质，如缓激肽、一氧化氮、一氧化碳和血管内皮生长因子；以及受损的淋巴回收。这些特征导致肿瘤组织显示出相当多的血浆成分和纳米药物的外渗。这些数据构成了开发大分子药物或纳米药物的基础理论。EPR 效应不一定适用于所有实体瘤，因为肿瘤血流量和血管通透性差异很大。随着肿瘤体积的增大，肿瘤血流量经常受阻，临床上经常可以看到这一点；早期、小肿瘤表现出更均匀的 EPR 效应，而晚期大肿瘤则表现出 EPR 效应的异质性。因此，在临床应用中应用 EPR 效应增强剂使 EPR 效应更加均匀是非常重要的。在这篇综述中，我们讨论了 EPR 效应：它的历史、涉及的因素、动力学和异质性。克服 EPR 效应异质性的策略可以保证更好的治疗效果，将药物输送到晚期癌症。
