The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application
Open accessAbstract
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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Many clinical cancers such as late-stage and refractory tumors are associated with poor blood flow due to coagulation and thrombi formation, exhibiting poor EPR effect.
“However, many clinical cancers such as late-stage tumors and refractory tumors are associated with poor blood flow due to the coagulation and thrombi formation exhibiting poor EPR effect [7,8,9,10,11,12].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [8]
Section 3 says abnormal tumor vessels obstruct blood flow, and Section 4.2 says blood flow is critical to nanomedicine delivery via the EPR effect (page numbers unavailable). The cited paper does not establish that coagulation or thrombi cause poor flow in late-stage or refractory tumors, or specifically link those tumor types to poor EPR. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe EPR effect can be enhanced by modifying vascular intermediaries such as angiotensin II, nitroglycerin or NO, CO, and enzyme inhibitors.
“The EPR effect can be enhanced by modifying vascular intermediaries such as angiotensin II, nitroglycerin or NO, CO, and enzyme inhibitors [7,8,9,10].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [8]
Section 4.1 says nitric oxide donors can enhance the EPR effect, and its cited references discuss nitroglycerin. Section 4.2 says angiotensin II increases tumor blood flow and drug delivery, but does not explicitly say it enhances the EPR effect. The passages do not establish CO or enzyme inhibitors as EPR-enhancing interventions. (LLM, conf=0.85)
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Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis
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- Authors
- Wu, J.
- Affiliations
- Beckman Research Institute (US)
- Corresponding author
- Wu, Jun
- ORCID
- Wu, Jun
- Venue
- Journal of Personalized Medicine
- Publisher
- MDPI AG
- Published
- 2021-08-06
- Volume
- 11
- Issue
- 8
- Pages
- 771
- ISSN
- 2075-4426 (ISSN-L)
- PMC
- PMC8402171
- OpenAlex
- W3191894985
- Cited by
- 1,030
- References
- 56
- Citations by year
- 2026: 230 · 2025: 318 · 2024: 224 · 2023: 165 · 2022: 86 · 2021: 7
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Personalized Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- enhanced permeability and retention effect, macromolecular drug delivery, albumin, solid tumors, tumor vascularization, nanomedicine, tumor perfusion
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