Strategies to improve the EPR effect: A mechanistic perspective and clinical translation
Strategies to improve the EPR effect: A mechanistic perspective and clinical translation
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DOI：
10.1016/j.jconrel.2022.03.043
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发表时间：
2022-03-28
影响因子：
10.8
通讯作者：
Mitragotri, Samir
中科院分区：
文献类型：
--
作者：
Ikeda-Imafuku, Mayumi;Wang, Lily Li-Wen;Mitragotri, Samir
已经进行了许多努力来实现抗癌药物的靶向递送以增强其功效并减少其副作用。这些努力包括纳米药物的开发，因为它们可以通过增强的渗透性和保留（EPR）效应选择性地穿透肿瘤血管。EPR效应于1986年由Maeda及其同事首次提出，此后人们开发了各种类型的纳米颗粒来利用这种现象进行药物输送。然而，EPR效应已被发现是高度可变的，因此由于复杂的肿瘤微环境而不可靠。已经探索了各种物理和药理学策略来克服这一挑战。在这里，我们审查的关键进展和新兴的概念，这样的EPR增强战略。此外，我们分析了723例含有EPR增强剂的纳米颗粒的临床试验，并讨论了它们的临床转化。
Many efforts have been made to achieve targeted delivery of anticancer drugs to enhance their efficacy and to reduce their adverse effects. These efforts include the development of nanomedicines as they can selectively penetrate through tumor blood vessels through the enhanced permeability and retention (EPR) effect. The EPR effect was first proposed by Maeda and co-workers in 1986, and since then various types of nanoparticles have been developed to take advantage of the phenomenon with regards to drug delivery. However, the EPR effect has been found to be highly variable and thus unreliable due to the complex tumor microenvironment. Various physical and pharmacological strategies have been explored to overcome this challenge. Here, we review key advances and emerging concepts of such EPR-enhancing strategies. Furthermore, we analyze 723 clinical trials of nanoparticles with EPR enhancers and discuss their clinical translation.