Multi-modal molecular imaging maps the correlation between tumor microenvironments and nanomedicine distribution
Open accessAbstract
Gaining insight into the heterogeneity of nanoparticle drug distribution within tumors would improve both design and clinical translation of nanomedicines.There is little data showing the spatio-temporal behavior of nanomedicines in tissues as current methods are not able to provide a comprehensive view of the nanomedicine distribution, released drug or its effects in the context of a complex tissue microenvironment.Methods: A new experimental approach which integrates the molecular imaging and bioanalytical technologies MSI and IMC was developed to determine the biodistribution of total drug and drug metabolite delivered via PLA-PEG nanoparticles and to overlay this with imaging of the nanomedicine in the context of detailed tumor microenvironment markers.This was used to assess the nanomedicine AZD2811 in animals bearing three different pre-clinical PDX tumors.Results: This new approach delivered new insights into the nanoparticle/drug biodistribution.Mass spectrometry imaging was able to differentiate the tumor distribution of co-dosed deuterated non-nanoparticle-formulated free drug alongside the nanoparticle-formulated drug by directly visualizing both delivery approaches within the same animal or tissue.While the IV delivered free drug was uniformly distributed, the nanomedicine delivered drug was heterogeneous.By staining for multiple biomarkers of the tumor microenvironment on the same tumor sections using imaging mass cytometry, co-registering and integrating data from both imaging modalities it was possible to determine the features in regions with highest nanomedicine distribution.Nanomedicine delivered drug was associated with regions higher in macrophages, as well as more stromal regions of the tumor.Such a comparison of complementary molecular data allows delineation of drug abundance in individual cell types and in stroma.Conclusions: This multi-modal imaging solution offers researchers a better understanding of drug and nanocarrier distribution in complex tissues and enables data-driven drug carrier design.
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By integration of molecular imaging and bioanalytical techniques, MSI and IMC determined biodistribution of drug and drug metabolites delivered via PLGA-PEG NPs and overlaid this with imaging of AZD2811 in context of TME markers in different PDX animal models.
“By integration of molecular imaging and bioanalytical techniques, MSI and IMC determined the biodistribution of drug and drug metabolites delivered via PLGA-PEG NPs and overlaid this with imaging of AZD2811 in the context of TME markers in different PDX animal models.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [144]
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Experimental — accuracy not yet measuredDelivered nanodrug was associated with tumor sites higher in macrophages, as well as high stromal regions.
“The delivered nanodrug was associated with tumor sites higher in macrophages, as well as high stromal regions [19,144].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [144]
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“The delivered nanodrug was associated with tumor sites higher in macrophages, as well as high stromal regions [19,144].”
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- Authors
- Strittmatter, N., Moss, J. I., Race, A. M., Sutton, D., Canales, J. R., Ling, S., Wong, E., Wilson, J., Smith, A., Howes, C., Bunch, J., Barry, S. T., Goodwin, R. J. A., & Ashford, M. B.
- Affiliations
- AstraZeneca (United Kingdom) (GB)
- Philipps University of Marburg (DE)
- AstraZeneca (United States) (US)
- National Physical Laboratory (GB)
- Corresponding author
- Goodwin, Richard J.A.
- Ashford, Marianne B.
- ORCID
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2022
- Volume
- 12
- Issue
- 5
- Pages
- 2162-2174
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC8899579
- OpenAlex
- W4212941728
- Cited by
- 25
- References
- 47
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 8
- FWCI
- 1.31
- 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)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- Funders
- Cancer Research UK (24034)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- tumor microenvironment, mass spectrometry imaging, imaging mass cytometry, tumor stroma, tumor-associated macrophages, deuterated drugs, drug metabolites, nanoparticle drug delivery
- MeSH terms
- Animals, Drug Carriers, Neoplasms, Tissue Distribution, Drug Delivery Systems, Nanomedicine, Nanoparticles, Molecular Imaging, Tumor Microenvironment
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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