Oxidized Activated Charcoal Nanozymes: Synthesis, and Optimization for In Vitro and In Vivo Bioactivity for Traumatic Brain Injury

Carbon‐based superoxide dismutase (SOD) mimetic nanozymes have recently been employed as promising antioxidant nanotherapeutics due to their distinct properties. The structural features responsible for the efficacy of these nanomaterials as antioxidants are, however, poorly understood. Here, the process–structure–property–performance properties of coconut‐derived oxidized activated charcoal (cOAC) nano‐SOD mimetics are studied by analyzing how modifications to the nanomaterial's synthesis impact the size, as well as the elemental and electrochemical properties of the particles. These properties are then correlated to the in vitro antioxidant bioactivity of poly(ethylene glycol)‐functionalized cOACs (PEG‐cOAC). Chemical oxidative treatment methods that afford smaller, more homogeneous cOAC nanoparticles with higher levels of quinone functionalization show enhanced protection against oxidative damage in bEnd.3 murine endothelioma cells. In an in vivo rat model of mild traumatic brain injury (mTBI) and oxidative vascular injury, PEG‐cOACs restore cerebral perfusion rapidly to the same extent as the former nanotube‐derived PEG‐hydrophilic carbon clusters (PEG‐HCCs) with a single intravenous injection. These findings provide a deeper understanding of how carbon nanozyme syntheses can be tailored for improved antioxidant bioactivity, and set the stage for translation of medical applications. Nanozymes synthesized via the oxidation of coconut‐derived activated charcoal afford markable protection against oxidative injury in an in vivo rat model of mild traumatic brain injury. By tuning the oxidation process, smaller, more homogeneous nanomaterials containing free‐radical‐quenching quinone active sites are targeted for enhanced bioactivity. Such findings highlight the features that drive the oxidative power of these nanozymes.