Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation

Hailiang Wu, Horacio Cabral, Kazuko Toh, Peng Mi, Yi Chun Chen, Yu Matsumoto, Naoki Yamada, Xueying Liu, Hiroaki Kinoh, Yutaka Miura, Mitsunobu R. Kano, Hiroshi Nishihara, Nobuhiro Nishiyama, Kazunori Kataoka

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29 Citations (Scopus)

Abstract

Nanocarriers have been used for specific delivery of therapeutic agents to solid tumors based on the enhanced permeability and retention in cancerous tissues. Despite metastasis is the main reason of cancer-related death and a priority for nanocarrier-based therapies, the targeting ability of nanocarriers to the metastatic disease is poorly understood, especially for preangiogenic micrometastases as nanocarriers usually use the malignant neovasculature for enhancing their accumulation. Thus, herein, we studied the ability of micellar nanocarriers incorporating (1,2-diaminocyclohexane)platinum(II) (DACHPt) for treating liver metastases of bioluminescent murine colon adenocarcinoma C-26, during overt and preangiogenic metastatic stages. After intravenous injection, DACHPt-loaded micelles (DACHPt/m) effectively inhibited the tumor growth in both metastatic tumor models. While the anticancer activity of the micelles against overt metastases was associated with their selective accumulation in cancerous tissues having neovasculature, the ability of DACHPt/m to target preangiogenic metastases was correlated with the inflammatory microenvironment of the niche. This targeting capability of polymeric micelles to preangiogenic metastasis may provide a novel approach for early diagnosis and treatment of metastases.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Controlled Release
Volume189
DOIs
Publication statusPublished - 2014 Sep 10
Externally publishedYes

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Keywords

  • Chemotherapy
  • Cyclooxygenase-2
  • Drug delivery system
  • Metastatic niche
  • Oxaliplatin

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Wu, H., Cabral, H., Toh, K., Mi, P., Chen, Y. C., Matsumoto, Y., Yamada, N., Liu, X., Kinoh, H., Miura, Y., Kano, M. R., Nishihara, H., Nishiyama, N., & Kataoka, K. (2014). Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation. Journal of Controlled Release, 189, 1-10. https://doi.org/10.1016/j.jconrel.2014.06.018