Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

Nanomedicine. 2012 Feb;8(2):136-46. doi: 10.1016/j.nano.2011.08.019. Epub 2011 Sep 17.

Abstract

The purpose of this work is to study the antimetastasis activity of gadolinium metallofullerenol nanoparticles (f-NPs) in malignant and invasive human breast cancer models. We demonstrated that f-NPs inhibited the production of matrix metalloproteinase (MMP) enzymes and further interfered with the invasiveness of cancer cells in tissue culture condition. In the tissue invasion animal model, the invasive primary tumor treated with f-NPs showed significantly less metastasis to the ectopic site along with the decreased MMP expression. In the same animal model, we observed the formation of a fibrous cage that may serve as a physical barrier capable of cancer tissue encapsulation that cuts the communication between cancer- and tumor-associated macrophages, which produce MMP enzymes. In another animal model, the blood transfer model, f-NPs potently suppressed the establishment of tumor foci in lung. Based on these data, we conclude that f-NPs have antimetastasis effects and speculate that utilization of f-NPs may provide a new strategy for the treatment of tumor metastasis.

From the clinical editor: In this study utilizing metallofullerenol nanoparticles, the authors demonstrate antimetastasis effects and speculate that utilization of these nanoparticles may provide a new strategy in metastatic tumor therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Female
  • Gadolinium / chemistry
  • Gadolinium / therapeutic use*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / secondary
  • Macrophages / chemistry
  • Macrophages / drug effects
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / metabolism
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Transplantation

Substances

  • Matrix Metalloproteinase Inhibitors
  • Gadolinium
  • Matrix Metalloproteinases