The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in <i>Cancer Research</i> as a new concept in cancer chemotherapy. My review here describes the his...

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Main Author: Hiroshi Maeda
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/11/3/229
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author Hiroshi Maeda
author_facet Hiroshi Maeda
author_sort Hiroshi Maeda
collection DOAJ
description This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in <i>Cancer Research</i> as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era.
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spelling doaj.art-def623d5eb4c49809793f86978348b192023-11-21T11:31:40ZengMDPI AGJournal of Personalized Medicine2075-44262021-03-0111322910.3390/jpm11030229The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future ProspectsHiroshi Maeda0BioDynamics Research Foundation, Kumamoto 862-0954, JapanThis Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in <i>Cancer Research</i> as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era.https://www.mdpi.com/2075-4426/11/3/229EPR effectenhanced permeability and retention effectnanomedicinescancer therapydrug deliverynanotechnology
spellingShingle Hiroshi Maeda
The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
Journal of Personalized Medicine
EPR effect
enhanced permeability and retention effect
nanomedicines
cancer therapy
drug delivery
nanotechnology
title The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
title_full The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
title_fullStr The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
title_full_unstemmed The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
title_short The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
title_sort 35th anniversary of the discovery of epr effect a new wave of nanomedicines for tumor targeted drug delivery personal remarks and future prospects
topic EPR effect
enhanced permeability and retention effect
nanomedicines
cancer therapy
drug delivery
nanotechnology
url https://www.mdpi.com/2075-4426/11/3/229
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