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Tumor targeting via EPR: Strategies to enhance patient responses
Open accessAbstract
The tumor accumulation of nanomedicines relies on the enhanced permeability and retention (EPR) effect. In the last 5-10 years, it has been increasingly recognized that there is a large inter- and intra-individual heterogeneity in EPR-mediated tumor targeting, explaining the heterogeneous outcomes of clinical trials in which nanomedicine formulations have been evaluated. To address this heterogeneity, as in other areas of oncology drug development, we have to move away from a one-size-fits-all tumor targeting approach, towards methods that can be employed to individualize and improve nanomedicine treatments. To this end, efforts have to be invested in better understanding the nature, the complexity and the heterogeneity of the EPR effect, and in establishing systems and strategies to enhance, combine, bypass and image EPR-based tumor targeting. In the present manuscript, we summarize key studies in which these strategies are explored, and we discuss how these approaches can be employed to enhance patient responses.
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“They showed around 97% of the NPs are delivered to tumors by endothelial cells through an active process of transcytosis instead of passive transport.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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“A recent study by Chan W.C.W et al. demonstrated that inter-endothelial gaps in tumors may not be responsible for the transport of nanodrugs into solid tumors [161].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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“Contrary to the EPR mechanism, the frequency of the gaps on the endothelial lining in tumors is too low to account for the NP accumulation in the tumor site, which was observed by TEM analysis [161].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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“Several studies have demonstrated that only 0.1 to 0.2% of the injected dose is efficient against tumor cells and exhibits significant anticancer effects [20,123,161].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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“Therefore, defining the dominant mechanism of the entry of NPs into tumors may help engineer effective delivery carriers to enhance cancer therapy [161].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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“This study’s outcome is a challenge for the long-established EPR mechanism of drug delivery to solid tumors.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [161]
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Metadata
- Authors
- Golombek, S. K., May, J.-N., Theek, B., Appold, L., Drude, N., Kiessling, F., & Lammers, T.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Utrecht University (NL)
- Corresponding author
- Lammers, Twan
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 130
- Pages
- 17-38
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC6130746
- OpenAlex
- W2884616676
- Cited by
- 1,262
- References
- 227
- Citations by year
- 2026: 118 · 2025: 115 · 2024: 121 · 2023: 124 · 2022: 200 · 2021: 261 · 2020: 221 · 2019: 93 · 2018: 7
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- University of Twente Research Information (submittedVersion, cc-by-nc-nd)
- Funders
- European Research Council (309495, 680882, 813086)
- German research Foundation (La2937/1-2, SFB/TRR57, SFB1066, GRK2375)
- European Union
- 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, tumor targeting, nanomedicine, tumor heterogeneity, precision oncology, tumor imaging, tumor accumulation
- MeSH terms
- Antineoplastic Agents, Humans, Neoplasms, Permeability, Drug Delivery Systems, Nanomedicine
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