Glucose-functionalized Iron Oxide Nanoparticles Which Co-conjugated with Hyaluronic Acid and Naringenin Induces ROS-mediated Apoptosis and Cell Cycle Arrest in Colon Cancer Cells

Articles in Press

Document Type : Research Article

Authors

1 Department of Biochemistry, NT.C., Islamic Azad University, Tehran, Iran

2 Department of Biology, Ra.C., Islamic Azad University, Rasht, Iran

Abstract

Targeted drug delivery has received attention in cancer chemotherapy. In the present study, glucose (Glu)-functionalized iron oxide nanoparticles (Fe3O4 NPs) were co-conjugated with hyaluronic acid (HA) and naringenin (NAR), and their anticancer potential against colon cancer cells was characterized. Properties of Fe3O4@Glu-HA-NAR NPs were investigated by SEM, DLS, zeta potential, FT-IR, and XRD analyses. Cytotoxicity of the NPs in HT-116 and HDF cell lines was investigated by an MTT assay. The effects of the Fe3O4@Glu-HA-NAR NPs on cell cycle and apoptosis/necrosis in HT-116 cell line was studied by flow cytometry. AO/PI staining and real-time PCR were employed to evaluate nuclear morphology and expression of caspase-8 gene in the cancer cells, and reactive oxygen species (ROS) levels were also determined. The Fe3O4@Glu-HA-NAR NPs exhibited spherical to cubic morphology, an average particle size of 77.6 nm, surface charge of -57.9 mV, hydrodynamic size of 783 nm, and structural characteristics similar to their constituent components. Fe3O4@Glu-HA-NAR nanoparticles demonstrated concentration-dependent cytotoxicity toward the studied cells with greater toxicity against HT-116 cells [50% inhibitory concentration (IC50) = 42.63 μg/mL]. In comparison, free NAR exhibited a higher IC₅₀ value (64.62 μg/mL), indicating that nanoparticle-mediated delivery enhanced the antiproliferative efficacy of NAR against colon cancer cells. Treatment of the HT-116 cells with Fe3O4@Glu-HA-NAR NPs blocked cell cycle progression at the S and G2/M phases, elevated cell necrosis and late apoptosis and caused nuclear alterations, including chromatin condensation. Exposure to Fe3O4@Glu-HA-NAR significantly upregulated the expression of the CASP-8 gene (3.8-fold) and increased ROS levels by 13.0-fold. This study demonstrates the promising potential of Fe3O4@Glu-HA-NAR NPs in targeting colon cancer cells.

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References

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