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

Lacy Reynolds, Rohit S. Mulik, Xiaodong Wen, Archana Dilip, Ian R. Corbin

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2123-2141
Number of pages19
JournalNanomedicine
Volume9
Issue number14
DOIs
StatePublished - Oct 1 2014

Keywords

  • Docosahexaenoic acid
  • Liver cancer
  • Low-density lipoprotein
  • Low-density lipoprotein receptor
  • Nanoparticle
  • Omega-3 fatty acids

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

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