Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target?
Open accessAbstract
Nano-sized therapeutic agents have several advantages over low molecular weight agents such as a larger loading capacity, the ability to protect the payload until delivery, more specific targeting due to multivalency and the opportunity for controlled/sustained release. However, the delivery of nano-sized agents into cancer tissue is problematic because it mostly relies on the enhanced permeability and retention (EPR) effect that depends on the leaky nature of the tumor vasculature and the prolonged circulation of nano-sized agents, allowing slow but uneven accumulation in the tumor bed. Delivery of nano-sized agents is dependent on several factors that influence the EPR effect; 1. Regional blood flow to the tumor, 2. Permeability of the tumor vasculature, 3. Structural barriers imposed by perivascular tumor cells and extracellular matrix, 4. Intratumoral pressure. In this review, these factors will be described and methods to enhance nano-agent delivery will be reviewed.
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The key success factor for theranostics in oncology is the presence of solid tumors with disrupted vascular architecture, which provides a pronounced EPR effect.
“The key success factor is the presence of solid tumors with disrupted vascular architecture, which provides a pronounced enhanced permeability and retention (EPR) effect [32,34].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [34]
Section 2.1 (page unavailable) describes abnormal, leaky tumor vessels that allow macromolecules to enter tumors, supporting the link between disrupted vasculature and EPR-based delivery. But the Introduction says EPR effects vary substantially among and within tumors, and Section 2.1 notes that high interstitial pressure can inhibit drug accumulation. The paper therefore does not establish that the presence of such tumors reliably produces a pronounced EPR effect or is the key success factor. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEPR effect can provide 20-30% increase in delivery compared with critical normal organs.
“Some reports have demonstrated that EPR effect can provide 20–30% increase in delivery compared with critical normal organs [157].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [157]
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“The key success factor is the presence of solid tumors with disrupted vascular architecture, which provides a pronounced enhanced permeability and retention (EPR) effect [32,34].”
- Authors
- Kobayashi, H., Watanabe, R., & Choyke, P. L.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kobayashi, Hisataka
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2014
- Volume
- 4
- Issue
- 1
- Pages
- 81-89
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC3881228
- OpenAlex
- W2116118767
- Cited by
- 996
- References
- 85
- Citations by year
- 2026: 29 · 2025: 59 · 2024: 76 · 2023: 79 · 2022: 79 · 2021: 93 · 2020: 119 · 2019: 114 · 2018: 113 · 2017: 85 · 2016: 79 · 2015: 55 · 2014: 15 · 2012: 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Theranostics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- enhanced permeability and retention effect, nanomedicine, tumor vasculature, tumor perfusion, tumor vascular permeability, extracellular matrix, anticancer drug delivery, nanoparticle targeting, sustained drug release
- MeSH terms
- Animals, Antineoplastic Agents, Capillary Permeability, Humans, Neoplasms, Tissue Distribution, Nanostructures
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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