Systemic targeting of lymph node metastasis through the blood vascular system by using size-controlled nanocarriers

Horacio Cabral, Jun Makino, Yu Matsumoto, Peng Mi, Hailiang Wu, Takahiro Nomoto, Kazuko Toh, Naoki Yamada, Yuriko Higuchi, Satoshi Konishi, Mitsunobu R. Kano, Hiroshi Nishihara, Yutaka Miura, Nobuhiro Nishiyama, Kazunori Kataoka

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66 Citations (Scopus)

Abstract

Occult nodal metastases increase the risk of cancer recurrence, demoting prognosis and quality of life of patients. While targeted drug delivery by using systemically administered nanocarriers can potentially control metastatic disease, lymph node metastases have been mainly dealt by locally injecting nanocarriers, which may not always be applicable. Herein, we demonstrated that sub-50 nm polymeric micelles incorporating platinum anticancer drugs could target lymph node metastases in a syngeneic melanoma model after systemic injection, even after removing the primary tumors, limiting the growth of the metastases. By comparing these micelles with clinically used doxorubicin-loaded liposomes (Doxil) having 80 nm, as well as a 70 nm version of the micelles, we found that the targeting efficiency of the nanocarriers against lymph node metastases was associated with their size-regulated abilities to extravasate from the blood vasculature in metastases and to penetrate within the metastatic mass. These findings indicate the potential of sub-50 nm polymeric micelles for developing effective conservative treatments against lymph node metastasis capable of reducing relapse and improving survival.

Original languageEnglish
Pages (from-to)4957-4967
Number of pages11
JournalACS Nano
Volume9
Issue number5
DOIs
Publication statusPublished - May 26 2015

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Keywords

  • Doxil
  • intravital microscopy
  • lymph node metastasis
  • melanoma
  • oxaliplatin
  • polymeric micelles

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Cabral, H., Makino, J., Matsumoto, Y., Mi, P., Wu, H., Nomoto, T., Toh, K., Yamada, N., Higuchi, Y., Konishi, S., Kano, M. R., Nishihara, H., Miura, Y., Nishiyama, N., & Kataoka, K. (2015). Systemic targeting of lymph node metastasis through the blood vascular system by using size-controlled nanocarriers. ACS Nano, 9(5), 4957-4967. https://doi.org/10.1021/nn5070259