MXene Biocompatibility Depending on Flake Size and Oxidation State

Over the last decade and a half, there has been a marked increase in the study of two-dimensional (2D) materials due to their exceptional physicochemical properties. Transition metal carbides, nitrides, and carbonitrides, collectively known as MXenes, were introduced at Drexel University in 2011 by Yury Gogotsi and Michel Barsoum. This emerging group of 2D materials has shown considerable promise in a variety of applications, including lithium and sodium-ion batteries, electrocatalysis, optoelectronic devices, flexible electronics, and healthcare sectors such as cancer treatment, bacteriology, immunology, targeted drug delivery, and tissue engineering. Research into the use of MXenes in biological and medical contexts is crucial for enhancing our knowledge and utilization of innovative materials in health and biotechnological advancements. Investigating biocompatibility and cellular response is crucial for the application of materials in medicine. Despite numerous publications and the established biocompatibility of MXenes, conflicting information regarding their safety persists. The primary reason for the contradictory data on MXene toxicity is the lack of control over their structural and chemical characteristics during biomedical research. Key factors such as flake size, chemical termination, and oxidation states can significantly influence MXene biocompatibility. Considering these aspects, we conducted a comprehensive study on MXene biocompatibility, focusing on their structural and chemical parameters.

Ti3C2, Ti3(CN)2, V2C, and Nb2C MXenes with controlled size, oxidation state, and chemical terminations were provided by Carbone-Ukraine. In this study, we assessed the biocompatibility and cellular response of these MXenes. We utilized the resazurin reduction metabolic assay, flow cytometry with Annexin V/PI for biocompatibility evaluation, BRDU-ELISA assay for proliferation analysis, and ROS generation measurement with 2',7'-dichlorofluorescin diacetate (DCFDA). Human Immortalized Keratinocytes (HaCaT) and Human Melanoma cells (MaMel8bIV) were used in the experiments.

Our data demonstrated that all types of MXenes exhibited high biocompatibility with dose-dependent effects. Ti3C2 and V2C MXenes at concentrations above 50 µg/ml showed moderate toxicity, indicating they can be used in biomedical research with certain limitations. The size of MXene flakes can significantly increase toxicity and impact cell metabolism, including extensive ROS generation. Additionally, oxidized materials can affect cell growth and proliferation, which must be considered during their applications.

Overall, our data demonstrate that controlling the size, chemical terminations, and oxidation state of MXenes is crucial for their safe application in biomedical research.