On tuning the cytotoxicity of Ti3C2 (MXene) flakes to cancerous and benign cells by post-delamination surface modifications

Abstract

Despite intensive research on the application of two-dimensional (2D) materials, including MXenes, in nanomedicine, the knowledge concerning the mechanisms responsible for their observed bio-effects is far from being understood. Here we present insight into the mechanism of toxicity in vitro of the 2D Ti3C2 MXene. The most important results of this work are that using simple, inexpensive, post-delamination treatments, such as ultrasonication or mild thermal oxidation it is possible to 'tune' the cytotoxicity of the Ti3C2Tz flakes. Sonication of Ti3C2Tz flakes, or sonication followed by mild oxidation in the water at 60 °C, renders them selectively toxic to cancer cells as compared to non-malignant ones. It relates to the appearance of superficial titanium (III) oxide (Ti2O3) layer corresponding to the type of post-treatment. The presence of surface-Ti2O3 results in a noticeably higher generation of oxidative stress compared to pristine 2D Ti3C2. Our findings give evidence that the sonication and thermal treatments were successful in changing the nature of the surface terminations on the Ti3C2Tz surfaces. This study makes a significant contribution to the future rationalized surface-management of 2D Ti3C2 MXene as well as encourages new rationalized applications in biotechnology and nanomedicine. Bullet points: 1. First study on 2D Ti3C2 MXene superficially oxidized to titanium (III) oxide i.e. Ti2O3. 2. By sonication Ti3C2Tz MXene flakes followed by mild thermal oxidation in the water at 60 °C for 24 h, it is possible to 'tune' the toxicity of the flakes to cancerous cell lines. 3. Decreases in cell viabilities were dose-dependent. 4. Highest cytotoxic effect was observed for thermally oxidized samples. 5. The thermally oxidized samples were also selectively toxic towards all cancerous cell lines up to 375 mg l-1. 6. Reactive oxygen species generation was identified as a mechanism of toxicity.