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 enhances 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.

增强的渗透性和保留 (EPR) 效应是实体瘤的一种独特现象，与其特定的解剖学和病理生理学特征有关，例如有缺陷的血管结构；血管内皮细胞之间的间隙大；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；和受损的淋巴恢复。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外渗。这些数据构成了大分子药物或纳米药物开发的基础理论。EPR效应不一定对所有实体瘤都有效，因为肿瘤血流量和血管通透性差异很大。正如临床上常见的那样，随着肿瘤大小的增加，肿瘤血流经常受阻；早期，小肿瘤表现出更均匀的EPR效应，而晚期大肿瘤表现出EPR效应的异质性。因此，在临床环境中应用增强EPR效应以使EPR效应更加均匀将是非常重要的。在这篇综述中，我们讨论了 EPR 效应：它的历史、涉及的因素以及动态和异质性。克服 EPR 效应异质性的策略可以保证药物递送至晚期癌症的更好治疗结果。