Enhanced Biocompatibility by Evaluating the Cytotoxic and Genotoxic Effects of Magnetic Iron Oxide Nanoparticles and Chitosan on Hepatocellular Carcinoma Cells (HCC)

Heba M Fahmy; Samar Shekewy; Fathi A Elhusseiny; Ahmed Elmekawy

doi:10.1007/s12013-024-01256-2

Enhanced Biocompatibility by Evaluating the Cytotoxic and Genotoxic Effects of Magnetic Iron Oxide Nanoparticles and Chitosan on Hepatocellular Carcinoma Cells (HCC)

Cell Biochem Biophys. 2024 Apr 1. doi: 10.1007/s12013-024-01256-2. Online ahead of print.

Authors

Heba M Fahmy¹, Samar Shekewy^{2

3}, Fathi A Elhusseiny², Ahmed Elmekawy⁴

Affiliations

¹ Biophysics Department, Faculty of Science, Cairo University, Cairo, Egypt.
² Physics Department, Faculty of Science, Tanta University, Tanta, Egypt.
³ Physics Department, Faculty of Science, Menofia University, Menofia, Egypt.
⁴ Physics Department, Faculty of Science, Tanta University, Tanta, Egypt. ahmed.elmakawi@science.tanta.edu.eg.

PMID: 38558242
DOI: 10.1007/s12013-024-01256-2

Abstract

Hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, is influenced by a myriad of clinic-pathological factors, including viral infections and genetic abnormalities. This study delineates the synthesis, characterization, and the biological efficacy of iron oxide nanoparticles (Fe₃O₄) and chitosan-coated iron oxide nanoparticles (Fe₃O₄-CS) against HCC. Analytical methods confirmed the successful synthesis of both nanoparticles, with Fe₃O₄-CS demonstrating a smaller, uniform spherical morphology and distinct surface and magnetic properties attributable to its chitosan coating. The prepared materials were analyzed using various techniques, and their potential cytotoxic effects on HepG2 cancer cells line for HCC were investigated. In biological evaluations against HepG2 cells, a notable distinction in cytotoxicity was observed. Fe₃O₄ showed modest anticancer activity with an IC50 of 383.71 ± 23.9 µg/mL, whereas Fe₃O₄ exhibited a significantly enhanced cytotoxic effect, with a much lower IC50 of 39.15 ± 39.2 µg/mL. The Comet assay further evidenced Fe₃O₄-CS potent DNA damaging effect, showcasing its superior ability to induce apoptosis through extensive DNA fragmentation. Biochemical analyses integrated into our results reveal that Fe₃O₄-CS not only induces significant DNA damage but also markedly alters oxidative stress markers. Compared to control and Fe₃O₄-treated cells, Fe₃O₄-CS exposure significantly elevated levels of oxidative stress markers: superoxide dismutase (SOD) increased to 192.07 U/ml, catalase (CAT) decreased to 0.03 U/L, glutathione peroxidase (GPx) rose dramatically to 18.76 U/gT, and malondialdehyde (MDA) levels heightened to 30.33 nmol/gT. These results underscore the potential of Fe₃O₄-CS nanoparticles not only in inducing significant DNA damage conducive to cancer cell apoptosis but also in altering enzymatic activities and oxidative stress markers, suggesting a dual mechanism of action that may underpin their therapeutic advantage in cancer treatment. Our findings advocate for the further exploration of Fe₃O₄-CS nanoparticles in the development of anticancer drugs, emphasizing their capability to trigger oxidative stress and enhance antioxidant defense mechanisms.

Keywords: Comet assay; Fe3O4 nanoparticles; Fe3O4-CS nanocomposite; HCC (HepG2); Oxidative and antioxidative stress markers.