The entry of nanoparticles into solid tumours

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...

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Veröffentlicht in:Nature materials Jg. 19; H. 5; S. 566 - 575
Hauptverfasser: Sindhwani, Shrey, Syed, Abdullah Muhammad, Ngai, Jessica, Kingston, Benjamin R., Maiorino, Laura, Rothschild, Jeremy, MacMillan, Presley, Zhang, Yuwei, Rajesh, Netra Unni, Hoang, Tran, Wu, Jamie L. Y., Wilhelm, Stefan, Zilman, Anton, Gadde, Suresh, Sulaiman, Andrew, Ouyang, Ben, Lin, Zachary, Wang, Lisheng, Egeblad, Mikala, Chan, Warren C. W.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.05.2020
Nature Publishing Group
Schlagworte:
631/67/327
639/301/357/354
639/925/352/2733
639/925/930/2735
Animals
Biomaterials
Blood vessels
Cancer
Cell Line, Tumor
Chemistry and Materials Science
Computer simulation
Condensed Matter Physics
Endothelial cells
Gold - chemistry
Gold - pharmacokinetics
Gold - pharmacology
Humans
Imaging techniques
Materials Science
Metal Nanoparticles - chemistry
Metal Nanoparticles - therapeutic use
Mice
Mice, Inbred BALB C
Models, Biological
Nanoparticles
Nanotechnology
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
Optical and Electronic Materials
Transport
Tumor Microenvironment - drug effects
Tumors
Xenograft Model Antitumor Assays
ISSN:1476-1122, 1476-4660, 1476-4660
Online-Zugang:Volltext
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Zusammenfassung: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. The dominant mechanism of nanoparticle entry into solid tumours has now been shown to be an active trans-endothelial pathway rather than the currently established passive transport via inter-endothelial gaps.
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ISSN:1476-1122
1476-4660
1476-4660
DOI:10.1038/s41563-019-0566-2