Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

Y. Matsumoto, Joseph W. Nichols, Kazuko Toh, Takahiro Nomoto, Horacio Cabral, Yutaka Miura, R. James Christie, Naoki Yamada, Tadayoshi Ogura, Mitsunobu Kano, Yasuhiro Matsumura, Nobuhiro Nishiyama, Tatsuya Yamasoba, You Han Bae, Kazunori Kataoka

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named ‘eruptions’) into the tumour interstitial space. We propose that ‘dynamic vents’ form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

Original languageEnglish
JournalNature Nanotechnology
DOIs
Publication statusAccepted/In press - Feb 15 2016

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ASJC Scopus subject areas

  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Electrical and Electronic Engineering
  • Condensed Matter Physics
  • Atomic and Molecular Physics, and Optics

Cite this

Matsumoto, Y., Nichols, J. W., Toh, K., Nomoto, T., Cabral, H., Miura, Y., Christie, R. J., Yamada, N., Ogura, T., Kano, M., Matsumura, Y., Nishiyama, N., Yamasoba, T., Bae, Y. H., & Kataoka, K. (Accepted/In press). Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery. Nature Nanotechnology. https://doi.org/10.1038/nnano.2015.342