Chemical and Colloidal Dynamics of MnO₂ Nanosheets in Biological Media Relevant for Nanosafety Assessment

Many layered crystal phases can be exfoliated or assembled into ultrathin 2D nanosheets with novel properties not achievable by particulate or fibrous nanoforms. Among these 2D materials are manganese dioxide (MnO₂) nanosheets, which have applications in batteries, catalysts, and biomedical probes. A novel feature of MnO₂ is its sensitivity to chemical reduction leading to dissolution and Mn²⁺ release. Biodissolution is critical for nanosafety assessment of 2D materials, but the timing and location of MnO₂ biodissolution in environmental or occupational exposure scenarios are poorly understood. This work investigates the chemical and colloidal dynamics of MnO₂ nanosheets in biological media for environmental and human health risk assessment. MnO₂ nanosheets are insoluble in most aqueous phases, but react with strong and weak reducing agents in biological fluid environments. In vitro, reductive dissolution can be slow enough in cell culture media for MnO₂ internalization by cells in the form of intact nanosheets, which localize in vacuoles, react to deplete intracellular glutathione, and induce cytotoxicity that is likely mediated by intracellular Mn²⁺ release. The results are used to classify MnO₂ nanosheets within a new hazard screening framework for 2D materials, and the implications of MnO₂ transformations for nanotoxicity testing and nanosafety assessment are discussed.