Reactive oxygen species scavenging by hemin-based nanosheets reduces Parkinson's disease symptoms in an animal model

Mitochondrial damage mediated by reactive oxygen species (ROS) is a major contributory factor to Parkinson's disease (PD) pathogenesis. The use of hemin-based nanomaterials to control ROS production can protect against neurological damage. Here, we report the rational design of a uniform and water-soluble artificial nanozyme based on an ultrathin graphitic carbon nitride (g-C3N4) nanosheet with loaded hemin to reduce ROS and treat PD. The g-C(3)N(4)4 not only acted as a scaffold for hemin loading but also improved the stability, cytotoxicity, and catalytic action of hemin. The integration of g-C3N4 increased hemin's peroxidase activity by 31.7%, promoting effective oxidation of the substrate 3,3 & PRIME;,5,5 & PRIME;-tetramethybenzichne (TMB) in the presence of H2O2 to a blue colored solution after 10 min' incubation at room temperature. Moreover, CN-hemin exhibited good biocompatibility and could effectively scavenge intracellular ROS and reduce cytotoxicity induced by H2O2 and 6hydroxydopamine (6-OHDA). In vivo animal studies using nematode transgenic hus111 strain and 6-OHDA pretreated C. elegans wild-type Bristol (N2) as models further showed that CN-hemin extended their lifespan and restored dopamine-dependent behaviors such as area-restricted searching, ethanol avoidance, and the basal slowing response by reducing ROS-mediated neurotoxicity. Nanomaterials using CN-hemin enzyme mimicry have potential biomedical applications, including the treatment of PD and disorders related to ROS metabolism.