High-resolution 3D visualization of nanomedicine distribution in tumors
Open accessAbstract
To improve the clinical translation of anti-cancer nanomedicines, it is necessary to begin building specific insights into the broad concept of the Enhanced Permeability and Retention (EPR) effect, using detailed investigations of the accumulation, distribution and retention of nanomedicines in solid tumors.Nanomedicine accumulation in preclinical tumors has been extensively studied; however, treatment efficacy will be heavily influenced by both the quantity of drug-loaded nanomedicines reaching the tumor as well as their spatial distribution throughout the tumor.It remains a challenge to image the heterogeneity of nanomedicine distribution in 3 dimensions within solid tumors with a high degree of spatial resolution using standard imaging approaches.Methods: To achieve this, an ex vivo micro computed tomography (µCT) imaging approach was developed to visualize the intratumoral distribution of contrast agent-loaded PEGylated liposomes.Using this semi-quantitative method, whole 3-dimensional (3D) tumor liposome distribution was determined with 17 µm resolution in a phenotypically diverse panel of four preclinical xenograft and patient-derived explant (PDX) tumor models.Results: High-resolution ex vivo µCT imaging revealed striking differences in liposome distribution within tumors in four models with different vascular patterns and densities, stromal contents, and microenvironment morphologies.Following intravenous dosing, the model with the highest density of pericyte-supported vessels showed the greatest liposome accumulation, while the model with vessels present in regions of high α-smooth muscle actin (αSMA) content presented with a large proportion of the liposomes at depths beyond the tumor periphery.The two models with an unsupported vascular network demonstrated a more restricted pattern of liposome distribution.Conclusion: Taken together, vessel distribution and support (the latter indicative of functionality) appear to be key factors determining the accumulation and distribution pattern of liposomes in tumors.Our findings demonstrate that high-resolution 3D visualization of nanomedicine distribution is a useful tool for preclinical nanomedicine research, providing valuable insights into the influence of the tumor vasculature and microenvironment on nanomedicine localization.
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High-resolution ex vivo μ-CT was utilized to study spatial distribution of drugs in different tumor models.
“Further, high-resolution ex vivo μ-CT was utilized to study the spatial distribution of drugs in different tumor models [127].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [127]
The Discussion (page not specified) says the study used high-resolution ex vivo μ-CT to visualize liposome distribution across four tumor models. However, the Results section, “Selection of nanomedicine” (page not specified), identifies the liposomes as containing iohexol, a CT contrast agent, rather than a therapeutic drug. The method and range of tumor models are supported, but describing the measured distribution as that of drugs overstates what was imaged. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVessel spread and vessel support are significant factors for effective liposome aggregation in tumors.
“This study identified vessel spread and vessel support as significant factors for effective liposome aggregation in tumors.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [127]
This semiquantitative technique was utilized to determine whole 3D liposome distribution in tumors with 17 μm resolution in different PDX models.
“This semiquantitative technique was utilized to determine whole 3D liposome distribution in tumors with 17 μm resolution in different PDX models.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [127]
The microcomputed tomography imaging approach was established to image intratumoral distribution of contrast agent-loaded PEGylated liposomes.
“The microcomputed tomography (μ-CT) imaging approach was established to image the intratumoral distribution of contrast agent-loaded PEGylated liposomes.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [127]
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“Further, high-resolution ex vivo μ-CT was utilized to study the spatial distribution of drugs in different tumor models [127].”
MethodStrittmatter, N., Moss, J. I., Race, A. M., Sutton, D., Canales, J. R., Ling, S., Wong, E., Wilson, J., Smith, A., Howes, C., et al. (2022) · Theranostics · doi:10.7150/thno.68000 · Cited by 25 · see citing works
- Authors
- Moss, J. I., Barjat, H., Emmas, S.-A., Strittmatter, N., Maynard, J., Goodwin, R. J. A., Storm, G., Lammers, T., Puri, S., Ashford, M. B., & Barry, S. T.
- Affiliations
- AstraZeneca (United Kingdom) (GB)
- Utrecht University (NL)
- Corresponding author
- Moss, Jennifer I.
- ORCID
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2020
- Volume
- 10
- Issue
- 2
- Pages
- 880-897
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC6929971
- OpenAlex
- W2993972798
- Cited by
- 19
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 3
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Theranostics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Twente Research Information (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- Funders
- AstraZeneca
- European Commission (NSC4DIPG, EuroNanoMed-III: NSC4DIPG)
- Deutsche Forschungsgemeinschaft (SFB 1066, TRR57, 309495, SFB‐TRR57, GRK 2375, 331065168)
- National Science Council
- H2020 European Research Council (813086)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- enhanced permeability and retention effect, PEGylated liposomes, intratumoral drug distribution, micro-computed tomography, ex vivo imaging, tumor vasculature, tumor microenvironment, patient-derived xenografts, alpha-smooth muscle actin, solid tumors
- MeSH terms
- Animals, Contrast Media, Humans, Liposomes, Male, Neoplasms, Permeability, Mice, SCID, Imaging, Three-Dimensional, Xenograft Model Antitumor Assays, Cell Line, Tumor, Nanomedicine, Mice, Nanoparticles, X-Ray Microtomography, Tumor Microenvironment
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