Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors
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 a...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/12/1964 |
| _version_ | 1797456833202356224 |
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| author | Waliul Islam Takuro Niidome Tomohiro Sawa |
| author_facet | Waliul Islam Takuro Niidome Tomohiro Sawa |
| author_sort | Waliul Islam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:12:33Z |
| format | Article |
| id | doaj.art-0552736c13074b0f8ffc8bab2769ecc0 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T16:12:33Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-0552736c13074b0f8ffc8bab2769ecc02023-11-24T16:01:17ZengMDPI AGJournal of Personalized Medicine2075-44262022-11-011212196410.3390/jpm12121964Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid TumorsWaliul Islam0Takuro Niidome1Tomohiro Sawa2Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanFaculty of Advanced Science and Technology, Kumamoto University, Kumamoto 860-8555, JapanDepartment of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanIn 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.https://www.mdpi.com/2075-4426/12/12/1964polymer drugEPR-effecttumor blood flowEPR-effect enhancersBNCTPDT |
| spellingShingle | Waliul Islam Takuro Niidome Tomohiro Sawa Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors Journal of Personalized Medicine polymer drug EPR-effect tumor blood flow EPR-effect enhancers BNCT PDT |
| title | Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors |
| title_full | Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors |
| title_fullStr | Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors |
| title_full_unstemmed | Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors |
| title_short | Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors |
| title_sort | enhanced permeability and retention effect as a ubiquitous and epoch making phenomenon for the selective drug targeting of solid tumors |
| topic | polymer drug EPR-effect tumor blood flow EPR-effect enhancers BNCT PDT |
| url | https://www.mdpi.com/2075-4426/12/12/1964 |
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