Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells

Nanomedicine (Lond). 2014 Jul;9(14):2123-41. doi: 10.2217/nnm.13.187. Epub 2014 Jan 7.

Abstract

Aim: The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells.

Materials & methods: LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively.

Results & discussion: The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose-response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity.

Conclusion: In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma.

Keywords: docosahexaenoic acid; liver cancer; low-density lipoprotein; low-density lipoprotein receptor; nanoparticle; omega-3 fatty acids.

Publication types

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

MeSH terms

  • Animals
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Coculture Techniques
  • Docosahexaenoic Acids / pharmacology*
  • Lipoproteins, LDL / administration & dosage*
  • Liver Neoplasms, Experimental / pathology*
  • Mice

Substances

  • Lipoproteins, LDL
  • Docosahexaenoic Acids