The entry of nanoparticles into solid tumours
Abstract
The concept of nanoparticle transport through gaps between endothelial cells (inter-endothelial gaps) in the tumour blood vessel is a central paradigm in cancer nanomedicine. The size of these gaps was found to be up to 2,000 nm. This justified the development of nanoparticles to treat solid tumours as their size is small enough to extravasate and access the tumour microenvironment. Here we show that these inter-endothelial gaps are not responsible for the transport of nanoparticles into solid tumours. Instead, we found that up to 97% of nanoparticles enter tumours using an active process through endothelial cells. This result is derived from analysis of four different mouse models, three different types of human tumours, mathematical simulation and modelling, and two different types of imaging techniques. These results challenge our current rationale for developing cancer nanomedicine and suggest that understanding these active pathways will unlock strategies to enhance tumour accumulation.
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Transcytosis is a metabolically active process that necessitates endothelial cells to reorganize their cytoskeleton and cell membrane, involving vesicle formation transporting NPs through the cytoplasm.
“Transcytosis is a metabolically active process that necessities endothelial cells to reorganize their cytoskeleton and cell membrane, involving vesicle formation transporting NPs through the cytoplasm [123,162].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [162]
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- Authors
- Sindhwani, S., Syed, A. M., Ngai, J., Kingston, B. R., Maiorino, L., Rothschild, J., MacMillan, P., Zhang, Y., Rajesh, N. U., Hoang, T., Wu, J. L. Y., Wilhelm, S., Zilman, A., Gadde, S., Sulaiman, A., Ouyang, B., Lin, Z., Wang, L., Egeblad, M., & Chan, W. C. W.
- Affiliations
- University of Toronto (CA)
- Cold Spring Harbor Laboratory (US)
- University of Oklahoma (US)
- University of Ottawa (CA)
- Corresponding author
- Chan, Warren C. W.
- ORCID
- Venue
- Nature Materials
- Published
- 2020-01-13
- Volume
- 19
- Issue
- 5
- Pages
- 566-575
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- OpenAlex
- W2998882776
- Cited by
- 1,732
- References
- 57
- Citations by year
- 2026: 235 · 2025: 248 · 2024: 233 · 2023: 263 · 2022: 264 · 2021: 299 · 2020: 188 · 2014: 1
- FWCI
- 66.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Funders
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada
- Gouvernement du Canada | Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council
- Northwell Health
- US Department of Defence, BCRP, Era of Hope Scholar
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- solid tumors, tumor vasculature, cancer nanomedicine, tumor accumulation, tumor microenvironment, nanoparticle extravasation
- MeSH terms
- Animals, Gold, Humans, Mice, Inbred BALB C, Models, Biological, Neoplasms, Experimental, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Metal Nanoparticles, Tumor Microenvironment
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