International Journal of Nanomedicine (Jul 2024)
Fe3O4-Coated CNTs-Gum Arabic Nano-Hybrid Composites Exhibit Enhanced Anti-Leukemia Potency Against AML Cells via ROS-Mediated Signaling
Abstract
Alyaa S Abdel Halim,1 Mohamed AM Ali,2,1 Fawad Inam,3,4 Abdulrahman M Alhalwan,5 Walid M Daoush5,6 1Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt; 2Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Kingdom of Saudi Arabia; 3Department of Engineering and Computing, School of Architecture, Computing and Engineering, University of East London, London, UK; 4Executive Principal Office, Oxford Business College, Oxford, OX1 2EP, UK; 5Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11623, Kingdom of Saudi Arabia; 6Department of Production Technology, Faculty of Technology and Education, Helwan University, Cairo, 11281, EgyptCorrespondence: Walid M Daoush, Email [email protected]: Prior studies on magnetite (Fe3O4) 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 Fe3O4 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+ cells. The molecular pathways of nanostructures’ cytotoxicity were also investigated.Results: The Fe3O4 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 IC50 values ranging from 42.437 to 189.842 μg/mL, they exhibited comparatively modest toxicity towards normal hematopoietic cells (IC50: 113.529‒162.656 μg/mL). The incorporation of Fe3O4 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 Fe3O4 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
