Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size

H. Cabral, Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M. R. Kano, K. Miyazono, M. Uesaka, N. Nishiyama, K. Kataoka

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1363 Citations (Scopus)

Abstract

A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β 2 inhibitor to increase the permeability of the tumours.

Original languageEnglish
Pages (from-to)815-823
Number of pages9
JournalNature Nanotechnology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

ASJC Scopus subject areas

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

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  • Cite this

    Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M., Terada, Y., Kano, M. R., Miyazono, K., Uesaka, M., Nishiyama, N., & Kataoka, K. (2011). Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nature Nanotechnology, 6(12), 815-823. https://doi.org/10.1038/nnano.2011.166