Zileuton™ loaded in polymer micelles effectively reduce breast cancer circulating tumor cells and intratumoral cancer stem cells

Nanomedicine. 2020 Feb:24:102106. doi: 10.1016/j.nano.2019.102106. Epub 2019 Oct 27.

Abstract

Tumor recurrence, metastatic spread and progressive gain of chemo-resistance of advanced cancers are sustained by the presence of cancer stem cells (CSCs) within the tumor. Targeted therapies with the aim to eradicate these cells are thus highly regarded. However, often the use of new anti-cancer therapies is hampered by pharmacokinetic demands. Drug delivery through nanoparticles has great potential to increase efficacy and reduce toxicity and adverse effects. However, its production has to be based on intelligent design. Likewise, we developed polymeric nanoparticles loaded with Zileuton™, a potent inhibitor of cancer stem cells (CSCs), which was chosen based on high throughput screening. Its great potential for CSCs treatment was subsequently demonstrated in in vitro and in in vivo CSC fluorescent models. Encapsulated Zileuton™ reduces amount of CSCs within the tumor and effectively blocks the circulating tumor cells (CTCs) in the blood stream and metastatic spread.

Keywords: Cancer stem cells (CSC); Circulating tumor tells (CTC); Nanomedicine; Polymeric micelles; Zileuton™.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / chemistry
  • Hydroxyurea / pharmacology
  • MCF-7 Cells
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Micelles*
  • Neoplastic Cells, Circulating* / metabolism
  • Neoplastic Cells, Circulating* / pathology
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Micelles
  • zileuton
  • Hydroxyurea