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Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors

期刊

JOURNAL OF PERSONALIZED MEDICINE
卷 12, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/jpm12121964

关键词

polymer drug; EPR-effect; tumor blood flow; EPR-effect enhancers; BNCT; PDT

资金

  1. Japan Society for the Promotion of Science [P21407]
  2. JST CREST [JPMJCR18H5]

向作者/读者索取更多资源

This article provides an overview of the development of the first polymer drug, SMANCS, in 1979, and the discovery of the enhanced permeability and retention effect (EPR effect) in 1986. The article discusses the application of EPR effect in nanomedicine and recent research progress.
In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with accumulation of the parental drug NCS. This momentous result led to discovery of the enhanced permeability and retention effect (EPR effect) in 1986. Later, the EPR effect became known worldwide, especially in nanomedicine, and is still believed to be a universal mechanism for tumor-selective accumulation of nanomedicines. Some research groups recently characterized the EPR effect as a controversial concept and stated that it has not been fully demonstrated in clinical settings, but this erroneous belief is due to non-standard drug design and use of inappropriate tumor models in investigations. Many research groups recently provided solid evidence of the EPR effect in human cancers (e.g., renal and breast), with significant diversity and heterogeneity in various patients. In this review, we focus on the dynamics of the EPR effect and restoring tumor blood flow by using EPR effect enhancers. We also discuss new applications of EPR-based nanomedicine in boron neutron capture therapy and photodynamic therapy for solid tumors.

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