[O.sub.4]-Coated CNTs-Gum Arabic Nano-Hybrid Composites Exhibit Enhanced Anti-Leukemia Potency Against AML Cells via ROS-Mediated Signaling

Background: Prior studies on magnetite ([Fe.sub.3][O.sub.4]) NPs and carbon nanotubes (CNTs) cytotoxic effects against acute myeloid leukemia (AML) are inconclusive rather than definitive. Purpose: Investigation of the effects of Gum Arabic (GA)-stabilized/destabilized [Fe.sub.3][O.sub.4] NPs and CNTs, alone or in combination, on AML cell proliferation. Methods: Hybrid NPs were synthesized, characterized, and assessed for their cytotoxicity against Kasumi-1, HL-60, and THP-1 in comparison to normal primary bone marrow [CD34.sup.+] cells. The molecular pathways of nanostructures' cytotoxicity were also investigated. Results: The [Fe.sub.3][O.sub.4] NPs were effectively synthesized and attached to the surface of the CNTs, resulting in the formation of a novel hybrid through their interaction with the GA colloidal solution in an aqueous media. Although the evaluated nanostructured nanoparticles had significant growth suppression ability against the leukemia cell lines, with [IC.sub.50] values ranging from 42.437 to 189.842 [micro]g/mL, they exhibited comparatively modest toxicity towards normal hematopoietic cells ([IC.sub.50]: 113.529-162.656 [micro]g/mL). The incorporation of [Fe.sub.3][O.sub.4] NPs with CNTs in a hybrid nanocomposite significantly improved their effectiveness against leukemia cells, with the extent of improvement varying depending on the specific cell type. The nanostructured particles were stabilized by GA, which enhances their ability to inhibit cell proliferation in a manner that depends on the specific cell type. Also, nanoparticles exhibit cytotoxicity due to their capacity to stimulate the production of intracellular ROS, halt the cell cycle at the G1 phase, and induce apoptosis. This is supported by the activation of p53, BAX, cytochrome C, and caspase-3, which are triggered by ROS. The nanostructures lead to an increase in the expression of genes encoding proteins related to oxidative stress (SIRT1, FOXO3, NFE2L2, and MAP3K5) and cyclin-dependent kinase inhibitors (CDKN1A and CDKN1B) in response to ROS. Conclusion: We provide an effective [Fe.sub.3][O.sub.4] NPs/CNTs nano-hybrid composite that induces apoptosis and has strong anti-leukemic capabilities. This hybrid nanocomposite is promising for in vivo testing and validation. Keywords: acute myeloid leukemia, anti-leukemic properties, carbon nanotubes, iron oxide nanoparticles, oxidative stress, reactive oxygen species