Metal-free hydrogen-bonded organic frameworks (HOFs) are porous materials formed through hydrogen bonding of organic components and exhibit excellent biocompatibility and enzyme compatibility in biomedical applications. However, it remains challenging to use HOFs to create multi-enzyme cascade antioxidant nanozymes for the treatment of cerebral ischemia-reperfusion injury (CIRI). Here, selenium-containing nano HOFs (SeHOFs) were synthesized as glutathione peroxidase mimics,Superoxide dismutase (SOD) and catalase (CAT) were encapsulated in situ to form a hybrid cascade antioxidant system (SeHOF@CAT@SOD). SeHOFs exhibited enhanced catalytic activity, preserved enzyme function, and could protect them from temperature, proteolysis, and denaturation. The metal-free nanoenzymes demonstrated excellent biocompatibility and cascade catalytic efficiency.It can scavenge reactive oxygen species and reduce cell apoptosis and ferroptosis in vitro. Peptide modification enhances accumulation at the infarct site, effectively reducing infarct volume, oxidative stress, neuronal apoptosis, ferroptosis, and inflammation in the CIRI model. This study highlights the potential of nano HOFs as a platform for developing advanced therapeutic nanoenzymes in the treatment of ischemic stroke.

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https://www.x-mol.com/paper/2008081716573552640/t?adv