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(H_(2)O_(2)),superoxide anion(O_(2)·^(-)),hydroxyl radical(·OH),nitric oxide(·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.