Development and use of ceramide nanoliposomes in cancer

Methods Enzymol. 2012:508:89-108. doi: 10.1016/B978-0-12-391860-4.00005-7.

Abstract

Integration of C₆-ceramide into stealth pegylated nanoliposomes has led to the development of a promising preclinical therapeutic alone and in combination with other agents for treatment of cancer. Ceramide itself has been implicated as a bioactive lipid second messenger mediating cell senescence, cell cycle arrest, and apoptosis. Recent lipidomic analyses have demonstrated that specific ceramide species are differentially metabolized in individual cancers. Therapeutics that increase ceramide levels in cancer tissues have shown increased cell death and tumor inhibition. However, the use of ceramide itself as therapeutic has been problematic due to its inherent hydrophobicity and insolubility, therefore limiting the application for intravenous administration. Pegylated nanoliposomes eliminate this issue and are able to enhance the intracellular delivery of ceramide to cancer cells.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Ceramides / administration & dosage*
  • Drug Carriers*
  • In Vitro Techniques
  • Liposomes*
  • Maximum Tolerated Dose
  • Membrane Potentials
  • Mice
  • Nanoparticles*
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Ceramides
  • Drug Carriers
  • Liposomes
  • Reactive Oxygen Species