Antitumor Activity of Chitosan-Coated Iron Oxide Nanocomposite Against Hepatocellular Carcinoma in Animal Models

Biol Trace Elem Res. 2023 Mar;201(3):1274-1285. doi: 10.1007/s12011-022-03221-7. Epub 2022 Jul 22.

Abstract

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. Chitosan-coated iron oxide nanocomposite (Fe3O4/Cs) is a promising bio-nanomaterial for many biological applications. The objective of this research was to evaluate the anticancer efficacy of Fe3O4/Cs against HCC in animal models. Fe3O4 nanoparticles were prepared and added to chitosan solution; then, the mixture was exposed to gamma radiation at a dose of 20 kGy. Rats have received diethylnitrosamine (DEN) orally at a dose of 20 mg/kg body weight 5 times per week during a period of 10 weeks to induce HCC and then have received Fe3O4/Cs intraperitoneal injection at a dose of 50 mg/kg body weight 3 times per week during a period of 4 weeks. After the last dose of Fe3O4/Cs administration, animals were sacrificed. DEN induced upregulation of PI3K/Akt/mTOR and MAPK (ERK, JNK, P38) signaling pathways and inflammatory markers (TLR4, iNOS, and TNF-α). DEN also decreases cleaved caspase-3 and increases liver enzymes (ALT, AST, and GGT) activities. Administration of Fe3O4/Cs significantly ameliorated the above-mentioned parameters.

Keywords: Gamma radiation; Hepatocellular carcinoma; Iron oxide nanocomposite; MAPK; PI3K/Akt/mTOR.

MeSH terms

  • Animals
  • Body Weight
  • Carcinoma, Hepatocellular* / chemically induced
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Chitosan* / pharmacology
  • Diethylnitrosamine
  • Liver Neoplasms* / chemically induced
  • Liver Neoplasms* / drug therapy
  • Models, Animal
  • Nanocomposites*
  • Phosphatidylinositol 3-Kinases
  • Rats

Substances

  • ferric oxide
  • Chitosan
  • Phosphatidylinositol 3-Kinases
  • Diethylnitrosamine