Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles
Open accessAbstract
Abstract Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally study the dynamics of the EPR effect upon single‐ and double‐dose nanotherapy with fluorophore‐labeled and paclitaxel‐loaded polymeric micelles. Using computed tomography‐fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR‐based tumor accumulation significantly increases during treatment, especially for more efficient double‐dose nanotaxane therapy. Furthermore, for double‐dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g–1) upon the first administration to 15% ID g–1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation.
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For dual dose treatment, tumor aggregation was enhanced over time, from 7% injected dose per gram upon the first administration to 15% injected dose per gram upon the fifth administration, contributing to efficient tumor growth inhibition.
“Further, for dual dose treatment, tumor aggregation was enhanced over time, from 7% injected dose per gram upon the first administration to 15% injected dose per gram upon the fifth administration, contributing to efficient tumor growth inhibition.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
The Results and Discussion report that, in the 30 mg kg⁻¹ group, accumulation per labeled injection rose from 7.2 to 14.7% ID g⁻¹; the third labeled injection was the fifth injection overall. The same section reports significant tumor-growth inhibition at that dose, but says improved tumor targeting only *seems* able to influence treatment outcomes. The claim presents that contribution more definitively than the paper does. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCancer nanodrugs rely on the EPR effect for effective accumulation into the target site.
“Cancer nanodrugs rely on the EPR effect for effective accumulation into the target site [2].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
The result demonstrated aggregation of micelles in tumors.
“The result demonstrated aggregation of micelles in tumors.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
Disproportionally more tumor accumulation was observed for double dose than single dose with an enhanced therapeutic effect.
“Disproportionally more tumor accumulation was observed for double dose than single dose with an enhanced therapeutic effect.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
Cy7-labeled and paclitaxel-loaded micelles were fabricated to longitudinally represent and enumerate nanomedicine tumor aggregation during nanotaxane therapy of 4T1 murine TNBC tumors.
“Cy7-labeled and paclitaxel-loaded micelles were fabricated to longitudinally represent and enumerate nanomedicine tumor aggregation during nanotaxane therapy of 4T1 murine TNBC tumors.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
Imaging tumor accumulation multiple times during therapy may be suitable for predicting therapy outcomes instead of imaging once at the beginning of treatment.
“Thus, imaging tumor accumulation multiple times during therapy may be suitable for predicting therapy outcomes instead of imaging once at the beginning of treatment [2].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
Heterogeneity in EPR-based tumor targeting was detected during nanodrug therapy.
“Heterogeneity in EPR-based tumor targeting was detected during nanodrug therapy.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [2]
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References 35 · Cited by 68
- Authors
- Biancacci, I., De Lorenzi, F., Theek, B., Bai, X., May, J., Consolino, L., Baues, M., Moeckel, D., Gremse, F., von Stillfried, S., El Shafei, A., Benderski, K., Azadkhah Shalmani, A., Wang, A., Momoh, J., Peña, Q., Buhl, E. M., Buyel, J., Hennink, W., Kiessling, F., Metselaar, J., Shi, Y., & Lammers, T.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Aachen 52074 Germany
- Institute of Pathology Medical Faculty RWTH Aachen University Clinic Aachen 52074 Germany
- Fraunhofer Institute for Molecular Biology and Applied Ecology (DE)
- Utrecht University (NL)
- Corresponding author
- Shi, Yang
- Lammers, Twan
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2022-01-24
- Volume
- 9
- Issue
- 10
- Pages
- e2103745-e2103745
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC8981450
- OpenAlex
- W4207051665
- Cited by
- 68
- References
- 35
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 20 · 2023: 13 · 2022: 3
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (GRK 2375, 331065168, SFB 1382, 403224013, SFB 1066, LA2937/4‐1, SH1223/1‐1)
- European Commission (EFRE‐0801767)
- European Research Council (864121)
- 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, polymeric micelles, paclitaxel, theranostics, individual heterogeneity, tumor growth inhibition, treatment outcome prediction
- MeSH terms
- Theranostic Nanomedicine, Humans, Micelles, Permeability, Nanomedicine, Nanoparticles
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