Tuning the transformation and cellular signaling of 2D titanium carbide MXenes using a natural antioxidant

2D titanium carbide (Ti₃C₂) MXenes have emerged as promising candidates for biomedical applications. However, the biological properties of these materials are poorly understood. Moreover, MXenes are prone to oxidation under ambient conditions. Here, we show that glutathione (GSH), a natural antioxidant present in millimolar concentrations in the cytosol of most cells, protects MXenes from oxidation in aqueous suspensions while preserving the biocompatibility of the material. Reactive molecular dynamics (RMD) simulations confirm that GSH protects MXenes. Moreover, we provide evidence of the intracellular biotransformation of Ti₃C₂ MXenes to the rutile form of TiO₂, and we show that GSH tunes the transformation process, resulting in the secretion of pro-inflammatory interleukin (IL)-1β through a non-canonical, elastase-dependent pathway. These results are important because they shed new light on the biotransformation of Ti₃C₂ MXenes and its ramifications for cellular signaling.