Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.
Keywords: Graphene oxide; autophagy; cancer cell killing; holo-transferrin; immobilization; intracellular ROS; lipid peroxidation.