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.
(January 2020)
The entry of nanoparticles into solid tumours.
Nat Mater.
ISSN 1476-1122
(Public Dataset)
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.
| Item Type: |
Paper
|
| Additional Information: |
Data Availability: All the annotated and analysed TEM images are uploaded on the Figshare server. This includes an Excel sheet that summarizes the results and overall analysis of the TEM images. This is available at https://doi.org/10.6084/m9.figshare.7485770. 3D images used in the simulations are also stored on Figshare and will be automatically downloaded by the code used for simulations. All other datasets generated and analysed during this study are available from the corresponding author upon reasonable request.
All code for simulations of nanoparticles in tumours can be found at https://github.com/jbRothschild/nano-extravasation. |
| Subjects: |
bioinformatics
diseases & disorders > cancer
diseases & disorders
diseases & disorders > neoplasms
bioinformatics > computational biology > algorithms
organism description > animal
therapies > cancer drugs - see diseases-cancer-drugs and therapies
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > computational biology
diseases & disorders > cancer > drugs and therapies
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions
organism description > animal > mammal > rodent
diseases & disorders > cancer > drugs and therapies > tumor microenvironment |
| CSHL Authors: |
|
| Communities: |
CSHL Cancer Center Program > Cellular Communication in Cancer Program
CSHL labs > Egeblad lab
School of Biological Sciences > Publications |
| Depositing User: |
Adrian Gomez
|
| Date: |
13 January 2020 |
| Date Deposited: |
15 Jan 2020 16:02 |
| Last Modified: |
01 Feb 2024 18:33 |
| Related URLs: |
|
| Dataset ID: |
- https://doi.org/10.6084/m9.figshare.7485770
- https://github.com/jbRothschild/nano-extravasation
|
| URI: |
https://repository.cshl.edu/id/eprint/38905 |
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