The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application.
The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application.
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DOI：
10.3390/jpm11080771
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发表时间：
2021-08-06
影响因子：
--
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wu J
实体瘤的化疗在临床上还远不能令人满意。尽管发现和合成了数十万种靶向癌细胞增殖和代谢中的各种关键单元的抗癌化合物，但根本问题是缺乏将这些化合物选择性靶向递送到实体瘤组织中以维持有效浓度水平一定时间长度以供药物-肿瘤相互作用执行抗癌活性。增强的渗透性和滞留效应（EPR效应）描述了一种普遍的病理生理学现象和机制，其中大分子化合物如白蛋白和超过一定尺寸（大于40 kDa）的其他聚合物缀合的药物可以在肿瘤血管化区域中逐渐积累，从而实现抗癌化合物靶向递送和滞留到实体瘤组织中。在临床实践中通过EPR效应的靶向治疗并不总是成功的，因为EPR效应的强度取决于肿瘤的类型和位置、肿瘤中血液灌注的状态以及大分子抗癌剂的物理化学性质而变化。本文综述了EPR效应的概念和机制的重要性，并讨论了如何更好地利用EPR效应开发更智能的大分子纳米药物，使其在临床应用中取得令人满意的结果。
Chemotherapy for human solid tumors in clinical practice is far from satisfactory. Despite the discovery and synthesis of hundreds of thousands of anticancer compounds targeting various crucial units in cancer cell proliferation and metabolism, the fundamental problem is the lack of targeting delivery of these compounds selectively into solid tumor tissue to maintain an effective concentration level for a certain length of time for drug-tumor interaction to execute anticancer activities. The enhanced permeability and retention effect (EPR effect) describes a universal pathophysiological phenomenon and mechanism in which macromolecular compounds such as albumin and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate in the tumor vascularized area and thus achieve targeting delivery and retention of anticancer compounds into solid tumor tissue. Targeting therapy via the EPR effect in clinical practice is not always successful since the strength of the EPR effect varies depending on the type and location of tumors, status of blood perfusion in tumors, and the physical-chemical properties of macromolecular anticancer agents. This review highlights the significance of the concept and mechanism of the EPR effect and discusses methods for better utilizing the EPR effect in developing smarter macromolecular nanomedicine to achieve a satisfactory outcome in clinical applications.
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DOI：
10.2217/17435889.3.5.703
发表时间：
2008-10
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Longmire M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
影响因子：
3
作者：
Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
15.9
作者：
Benjamin, LE;Golijanin, D;Keshet, E
通讯作者：
Keshet, E
DOI：
10.1016/0277-5379(83)90028-7
发表时间：
1983-01-01
期刊：
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY
影响因子：
--
作者：
KONNO, T;MAEDA, H;YOKOYAMA, I
通讯作者：
YOKOYAMA, I