Single-atom cobalt nanozymes promote spinal cord injury recovery by anti-oxidation and neuroprotection

Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury (SCI). Antioxidant therapies that reduce the reactive oxygen and nitrogen species (RONS) overgeneration and inflammation are proved promising for improving the outcomes. However, efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging. Here, a single-atom cobalt nanozyme (Co-SAzyme) with a hollow structure was reported to reduce the RONS and inflammation in the secondary injury of SCI. Among SAzymes featuring different single metal-N sites (e.g., Mn, Fe, Co, Ni, and Cu), this Co-SAzyme showed a versatile property to eliminate hydrogen peroxide (H2O2), superoxide anion (O-2-), hydroxyl radical (center dot OH), nitric oxide (center dot NO), and peroxynitrite (ONOO-) that overexpressed in the early stage of SCI. The porous hollow structure also allowed the encapsulation and sustained release of minocycline for neuroprotection in synergy. In vitro results showed that the Co-SAzyme reduced the apoptosis and pro-inflammatory cytokine levels of microglial cells under oxidative stress. In addition, the Co-SAzyme combined with minocycline achieved remarkable improved functional recovery and neural repairs in the SCI-rat model.

Automated summary

Oxidative stress and inflammation are key processes in traumatic spinal cord injury (SCI), and effective antioxidant therapy is challenging. Researchers developed a hollow Co-SAzyme, which effectively reduced reactive oxygen and nitrogen species (RONS) and inflammation in the secondary injury of SCI. The Co-SAzyme demonstrated versatile RONS elimination capabilities and facilitated sustained release of minocycline for neuroprotection. In vitro and in vivo experiments confirmed the Co-SAzyme's ability to reduce apoptosis and pro-inflammatory cytokines, and improve functional recovery and neural repairs in an SCI-rat model.