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

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.