Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration.

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.

Carbon nanosphere based bifunctional oxidoreductase nano-catalytic agent to mitigate hypoxia in cancer cells.

Developing metal-free carbon nanozyme for tumor hypoxia is difficult. In biomedical applications, especially in the case of biomolecular detection, extensive research has been done on nanozymes with enzyme-mimicking catalytic activity. However, there are considerably fewer investigations on targeted nano-catalytic tumor therapy. Nano catalytic medicine-enabled chemotherapy is a safe and promising treatment strategy that involves the conversion of excess H2O2 into O2 in a tumor environment. Here we have synthesized carbon nanosphere (CNS) using the Camellia sinensis plant (CS-CNS). Further surface functionalization was achieved via nitrilotriacetic acid conjugation (NTA@CS-CNS). A stability study of synthesized nanozyme in the presence of various cations, anions, and 5 different pH range suggested the robustness of carbon based nanoassembly. The catalytic in vitro study shows that NTA@CS-CNS mimics peroxidase and catalase using TMB and H2O2 as substrates. NTA@CS-CNS showed Km and Vmax values of ~ 193.2 µM and 0.43 µM/s, ~ 413 µM and 1.42 µM/s, and ~ 378 µM and 1.63 µM/s, respectively when H2O2 and TMB was used for CAT and POD activity. Results showed that NTA@CS-CNS in combination with SFN and laser irradiation reduces hypoxia. Hence, our study could pave the path for the development of different non-toxic nano catalytic therapy for tumors in cancerous cells.