Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review
Abstract
Most solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues or organs, such as extensive angiogenesis and hence hypervasculature, defective vascular architecture, impaired lymphatic drainage/recovery system, and greatly increased production of a number of permeability mediators. The phenomenon now known as the enhanced permeability and retention (EPR) effect for lipid and macromolecular agents has been observed to be universal in solid tumors. Primarily, enhanced vascular permeability will sustain an adequate supply of nutrients and oxygen for rapid tumor growth. The EPR effect also provides a great opportunity for more selective targeting of lipid- or polymer-conjugated anticancer drugs, such as SMANCS and PK-1, to the tumor. In the present review, the basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor. Tumor-specific vascular physiology is also described.
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Using simple, direct modulation of TRPV4 with GSK101 in a 3D microfluidic system, vascular integrity can be tuned to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, and achieve vascular leakiness comparable with previous MTM studies using tumor cells.
“Using this simple, direct modulation of TRPV4 with GSK101 in a 3D micro fl uidic system, we can therefore tune the vascular integrity to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, 28,30,51,52 and achieve vascular leakiness in a manner that is comparable with previous MTM studies using tumor cells. 2,53”
From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [2]
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- Authors
- Maeda, H., Wu, J., Sawa, T., Matsumura, Y., & Hori, K.
- Affiliations
- Kumamoto University (JP)
- National Cancer Center Hospital (JP)
- Tohoku University (JP)
- Corresponding author
- Maeda, H
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 65
- Issue
- 1-2
- Pages
- 271-284
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2002516695
- Cited by
- 6,565
- References
- 0
- Citations by year
- 2026: 166 · 2025: 214 · 2024: 215 · 2023: 251 · 2022: 294 · 2021: 335 · 2020: 378 · 2019: 306 · 2018: 386 · 2017: 438 · 2016: 433 · 2015: 407 · 2014: 418 · 2013: 419 · 2012: 393
- FWCI
- 27.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- enhanced permeability and retention effect, tumor vascular permeability, macromolecular therapeutics, solid tumors, tumor angiogenesis, tumor hypervascularity, anticancer drug delivery, SMANCS, tumor-specific targeting
- MeSH terms
- Animals, Antineoplastic Agents, Capillary Permeability, Humans, Neoplasms, Regional Blood Flow
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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