Critical Assessment of Intrinsic Antibacterial Properties and Photothermal Therapy Potential of MXene Nanosheets

MXenes are well-known as highly biocompatible two-dimensional nanomaterials with a wide range of biomedical applications, including antibacterial strategies. However, the coexistence of high biocompatibility and reported strong antibacterial effects presents a fundamental contradiction that requires critical evaluation. In this study, we systematically investigated the antibacterial properties of pure Ti₃C₂T _<i>x</i> , Nb₂CT _<i>x</i> , V₂CT _<i>x</i> , and Ti₃CNT _<i>x</i> MXene nanosheets of varying flake sizes using multiple in vitro assays and an in vivo wound model. High-resolution structural and chemical characterizations confirmed the use of high-quality, minimally oxidized MXene samples with well-defined surface terminations. Despite using multiple evaluation methods, including disk diffusion, broth microdilution, time-kill kinetics, ROS quantification, and electron microscopy, no significant antibacterial effects were observed at subtoxic concentrations. Furthermore, neither reactive oxygen species-mediated damage nor the hypothesized "nano-knife" mechanical disruption mechanism could be confirmed. This suggests that the previous observations of antibacterial properties resulted from incomplete removal of etching products or partial oxidation of MXene nanosheets. In contrast, we demonstrate that MXene-assisted photothermal therapy (PTT) under near-infrared laser irradiation offers highly effective and selective bacterial ablation. Ti₃C₂T _<i>x</i> MXene exhibited strong photothermal performance, achieving complete bacterial killing in vitro and significant wound healing efficacy in an in vivo rat model. Targeted PTT using antibody-functionalized MXene nanosheets enabled the eradication of <i>Escherichia coli</i> while sparing nontarget bacteria. These findings suggest that while intrinsic antibacterial properties of pristine MXenes are limited, their biocompatibility and photothermal responsiveness make them promising platforms for next-generation, externally triggered antibacterial therapies.