title: Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Lacy
authors.initials: L
authors.lastname: Reynolds
authors.forename: Rohit S
authors.initials: RS
authors.lastname: Mulik
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wen
authors.forename: Archana
authors.initials: A
authors.lastname: Dilip
authors.forename: Ian R
authors.initials: IR
authors.lastname: Corbin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D051379:Mice
chemical_list: D008077:Lipoproteins, LDL; D004281:Docosahexaenoic Acids
keywords: docosahexaenoic acid; liver cancer; low-density lipoprotein; low-density lipoprotein receptor; nanoparticle; omega-3 fatty acids