Functional Doxorubicin-Loaded Omega-3 Unsaturated Fatty Acids Nanoparticles in Reversing Hepatocellular Carcinoma Multidrug Resistance

Abstract

Background This study investigated a nanoparticle drug delivery system to reverse multidrug resistance (MDR) and assessed its anticancer efficacy in hepatocellular carcinoma (HCC). Material/Methods Docosahexaenoic acid (DHA) was used as the functional excipient and doxorubicin (DOX) as the chemotherapeutic drug to synthesize DOX nanoparticles (DOX-nano). The human HCC cell line HepG2 was used for experiments. HepG2/DOX, HepG2+DOX, HepG2+DOX-nano, HepG2/DOX+DOX, and HepG2/DOX+DOX-nano groups cells were treated with DOX or DOX-nano (5 μg/mL). Nude mice bearing a HepG2/DOX xenograft were divided into model, DOX, vector-nano, and DOX-nano groups and injected with saline, DOX reagent, vector-nano, and DOX-nano (2 mg/kg), respectively. Next, cytotoxicity, cellular uptake, cell apoptosis and migration, fluorescence imaging, TUNEL assay, and tumor inhibition effects were assessed in vitro and in vivo. Furthermore, expression of MDR-related proteins was also detected using western blotting. Results Fluorescence imaging showed that the DOX uptake in the DOX-nano-treated group was the strongest in the HCC cells or tumors. Cell apoptosis was significantly increased in DOX-nano-treated HepG2/DOX cells and tumors, and cell migration was significantly inhibited in the DOX-nano-treated HepG2/DOX cells compared with the other groups. The tumor inhibitory rate in DOX-nano-injected tumors was also significantly higher than in other groups. The expression of breast cancer resistance protein, B-cell lymphoma 2, lung resistance protein, multidrug resistance protein, and protein kinase C alpha was significantly decreased in DOX-nano-treated HepG2/DOX cells and xenograft tumors. Significantly better antitumor and MDR-reversing effects were also observed in the HepG2+DOX group compared with the HepG2/DOX group. Conclusions This study revealed the potential efficacy of a DOX-nano drug delivery system for the treatment of HCC, using HepG2/DOX cells and nude mice bearing HepG2/DOX xenografts.

[Retracted] Mendelian Randomization Study of Causal Relationship between Omega‐3 Fatty Acids and Risk of Lung Cancer

“…As immuno-nutrients, omega-3 fatty acids are often applied in nutritional treatment of cancer [ 41 ]. They exert a crucial role in cell signaling, cell structure, and cell membrane fluidity [ 42 ]. Furthermore, they mediate the resolution of inflammation, thereby exerting an anti-inflammation effect [ 43 ].…”

Natural Products for Liver Cancer Treatment: From Traditional Medicine to Modern Drug Discovery

“…Wang et al reported that doxorubicin-loaded docosahexaenoic acid nanoparticles (DOX-nano) significantly inhibited the tumor growth [ 19 ]. HepG2/DOX cells were injected into BALB/c mice, and after that, the mice were injected with DOX-nano at 2 mg/kg for 10 days.…”

Nutraceutical-Based Nanoformulations for Breast and Ovarian Cancer Treatment

“…The authors ascribed the enhanced antineoplastic effect to several factors, such as: (i) the increased lipophilicity of the nanoformulation, which improved the drug loading efficiency; (ii) the faster DOX release rate from the omega-3 PUFA nanosystem at pH 5.0 than at pH 7.4, that may potentially decrease the secondary toxic effects of this drug; and, finally, (iii) the improved uptake of DOX when delivered to the neoplastic cells through the hydrophobic-lipid rich nanosystem. However, they did not consider the recognized and more specific antineoplastic activities of these FAs, as well as the increased efficiency shown by DOX as it was combined with a concomitant treatment with omega-3 PUFAs, as previously reported by other authors [ 37 , 46 , 61 ].…”

“…The possible antineoplastic use of omega-3 PUFAs included in nanoformulations is still attracting great attention as demonstrated by the promising results obtained over the last few years in a large array of cancers, such as hepatocarcinoma [ 46 ], neuroblastoma [ 47 ], pancreatic cancer [ 48 ] and melanoma [ 49 ] (for a review, see [ 50 ]).…”