Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram

Nanotechnology. 2014 Mar 28;25(12):125102. doi: 10.1088/0957-4484/25/12/125102. Epub 2014 Feb 27.

Abstract

Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disulfiram / pharmacology*
  • Drug Delivery Systems / methods*
  • Endothelial Cells / drug effects
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Maleates / administration & dosage*
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • Oxidation-Reduction / drug effects*
  • Polystyrenes / administration & dosage*

Substances

  • Antineoplastic Agents
  • Maleates
  • Micelles
  • Polystyrenes
  • poly(styrene-co-maleic anhydride)
  • Disulfiram