Abstract
This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA–AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA–AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA–AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.
•The first time to study GA-AuNPs/laser effect on hepatic pre-neoplastic lesions•GA-AuNPs/laser can inhibit early initiation stage of carcinogenesis process.•GA-AuNPs/laser induced extrinsic apoptosis.•GA-AuNPs/laser increased death receptors DR5 and caspase-3.•GA-AuNPs/laser inhibited the preneoplastic lesions incidence, GST-P, and TNF-α.