Low-Density Lipoprotein-Mediated Delivery of Docosahexaenoic Acid Selectively Kills Murine Liver Cancer Cells

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.

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound

“…The zeta potential for these particles was slightly electronegative (-14.2 ± 1.4 mV, this slight change in surface charge relative to plasma LDL is typical for most modified/functionalized LDL nanoparticles. [29] The compositional make up of LDL-DiR nanoparticles contained an estimated 818 molecules of phospholipid, and 6 molecules of DiR per particle. Unlike, LDL-DHA, LDL-DiR does retain free or esterified cholesterol at its surface and in its core respectively.…”

“…[29] Briefly, LDL freeze dried in the presence of starch was subject to several rounds of organic extraction to remove nonpolar lipids from LDL. Thereafter, DHA (dissolved in heptane) was added to the LDL residue and incubated at 4°C for 90 min.…”

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

“…Much attention has been paid to the design of novel nanocarriers based on LDL, 18,19,31,32 due to the overexpression of LDLR in many tumor cells, which offers the advantage of tumor targeting for LDL-based nanocarriers. However, an LDL-based nanocarrier is less than ideal as a targeted drugdelivery system, not only because the quantity of natural LDL extracted from human serum is low but also because it is difficult to isolate the ApoB, which is large and aggregates easily during purification.…”

“…16 These findings show the potential of LDLR as a targeting receptor for the design of TNBC-targeted chemotherapy-delivery systems. Although many studies have exploited LDLR as a target for tumor diagnosis and treatment of diverse types of cancer, including brain glioma, liver cancer, lung cancer, prostate cancer, and colorectal cancer, 13,[17][18][19][20] few have extensively explored LDLR as a potential receptor for targeted therapy of TNBC.…”

Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications

“…To this end, Reynolds and coworkers incorporated DHA into LDL and further evaluated its cytotoxicity in both healthy (TIB-73) and malignant (TIB-75) murine liver cells. 36 At 60 µM of DHA-loaded LDL, TIB-75 cells were completely killed whereas TIB-73 cells remained viable. They precluded that the selective cytotoxicity was caused by the enhanced peroxidation of DHA and subsequent production of ROS in cancerous cells.…”