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

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

Author information

1
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.

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

PMID:
24397600
PMCID:
PMC4156561
DOI:
10.2217/nnm.13.187
[Indexed for MEDLINE]
Free PMC Article

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