Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors
Open accessAbstract
The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines.
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Various research groups have contributed to EPR effect enhancement by physical means such as mild hyperthermia, photodynamic activation, radiation therapy, and ultrasounds.
“Various research groups have contributed to the EPR effect enhancement strategies by employing physical means such as mild hyperthermia, photodynamic activation of tissues, radiation therapy, and ultrasounds [90,113,114,115,116,117,118,119].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [90]
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- Authors
- Ojha, T., Pathak, V., Shi, Y., Hennink, W. E., Moonen, C. T. W., Storm, G., Kiessling, F., & Lammers, T.
- Affiliations
- Utrecht University (NL)
- Universitätsklinikum Aachen (DE)
- University Medical Center Utrecht (NL)
- Corresponding author
- Kiessling, Fabian
- Lammers, Twan
- ORCID
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 119
- Pages
- 44-60
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC5919100
- OpenAlex
- W2727515347
- Cited by
- 260
- References
- 106
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 22 · 2023: 27 · 2022: 30 · 2021: 37 · 2020: 37 · 2019: 34 · 2018: 31 · 2017: 3
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- University of Twente Research Information (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- European Union (EU H2020-MSCA-ITN-2014 642 028-NABBA)
- European Research Council (309495, 680882)
- German Research Foundation (DFG La2937/1-2, SFB1066)
- German Academic Exchange Program (DAAD 57214224)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- enhanced permeability and retention effect, anticancer drug delivery, nanomedicine, vessel normalization, hyperthermia, radiotherapy, sonoporation, phototherapy, liposomes, polymers, micelles, tumor heterogeneity
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Neoplasms, Permeability, Drug Delivery Systems, Nanomedicine
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