In Vitro and In Vivo Synergistic Antitumor Activity of Albumin-Coated Oleic Acid-Loaded Liposomes toward Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The in vitro studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC₁₀₀ of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC₅₀ of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression ($>$7.0-fold), compared to OA. The in vivo study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the in vitro and in vivo chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.

Keywords:

• Hepatocellular carcinoma
• liposomes
• camel albumin
• oleic acid

Ethical approval

All methods were performed in accordance with the relevant guidelines and regulations, and the experiments done on animals are in accordance with arrival guidelines. The experimental design was accepted by the local research ethical committee (REC) of experimental animal use at the National Research Centre, Cairo, Egypt by applying the principles of replacement, reduction, and refinement (the 3Rs).

Author contributions

E.M.E.-F.: conceptualization, investigation, formal analysis, experimental details, writing-review, and editing the manuscript. M.A.: methodology, investigation, formal analysis, experimental details, writing review, and editing the manuscript. M.M.A.-S.: investigation, formal analysis, experimental details, writing review, and editing the manuscript. K.G.A.-W: investigation, formal analysis, experimental details, writing review, and editing the manuscript. D.G.E.-S.: methodology, writing - review & editing, H.E.-G.: investigation, formal analysis, experimental details, writing-review and editing the manuscript. All authors have read and agreed to the published version of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Data availability statement

The datasets used/or analyzed during the current study are available from the corresponding authors upon reasonable request.

Additional information

Funding

The study was funded by the Academy of Scientific Research and Technology (National Program for Research & Innovation in Health and Biomedical Sciences (PRISM_ 5126) program, Call no. 2/2019/ASRT-Health).