The reversal of drug resistance by two‐dimensional titanium carbide Ti(2)C (2D Ti2C) in non‐small‐cell lung cancer via the depletion of intracellular antioxidant reserves

BACKGROUND: Chemoresistance is a major barrier limiting the therapeutic efficacy of late stage non‐small cell lung cancer (NSCLC). In this study, we sought to use two‐dimensional titanium carbide (2D Ti(2)C) to reverse cisplatin resistance in NSCLC. METHODS: We first achieved favorable properties as a potential anti‐tumor agent. We then compared cell viability and cisplatin uptake in chemoresistant NSCLC cells before and after the use of 2D Ti(2)C. Afterwards, we explored the effects of 2D Ti(2)C on intracellular antioxidant reserves, followed by evaluating the subsequent changes in the expression of core drug resistance genes. Finally, we confirmed the tumor inhibitory effect and bio‐safety of 2D Ti(2)C in a drug‐resistant lung cancer model in nude mice. RESULTS: Due to the properties of thin layer, large specific surface area, and abundant reactive groups on the surface, 2D Ti(2)C can deplete the antioxidant reserve systems such as the glutathione redox buffer system, γ‐glutamylcysteine synthetase (γ‐GCS), glutathione peroxidase (GPx), glutathione‐S‐transferase‐Pi (GST‐π), and metallothionein (MT), thereby increasing the intracellular accumulation of cisplatin and decreasing the expression of drug resistance genes. CONCLUSIONS: 2D Ti(2)C can reverse NSCLC chemoresistance both in vitro and in vivo, suggesting that it may potentially become a novel and effective means to treat chemoresistant NSCLC in the clinic.