Calcium Hexacyanoferrate (III) Nanocatalyst Enables Redox Homeostasis for Autism Spectrum Disorder Treatment

Abstract Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder with considerable heterogeneity, in which over‐generated reactive oxygen species (ROS) induce a cascade of pathological changes, including cellular apoptosis and inflammatory responses. Given the complex etiology of ASD, no effective treatment is available for ASD. In this work, a specific catalytic nanoenzyme, calcium hexacyanoferrate (III) nanocatalysts (CaH NCs), is designed and engineered for efficient ASD treatment. CaH NCs can mimic the activities of natural enzymes including superoxide dismutase, peroxidase, catalase, and glutathione peroxidase, which mitigates intracellular excessive ROS and regulates redox equilibrium. These CaH NCs modulate mitochondrial membrane potential, elevate B‐cell lymphoma‐2 levels, and suppress pro‐apoptotic proteins, including Caspase‐3 and B‐cell lymphoma‐2‐associated X, thus effectively reducing cellular apoptosis. Importantly, CaH NCs alleviate inflammation by upregulating anti‐inflammatory cytokine interleukin‐10 and downregulating pro‐inflammatory factors, resulting in attenuated activation of microglial and astrocytic and subsequent reduction in neuroinflammation. Subsequently, CaH NCs enhance social abilities, decrease anxiety levels, ameliorate repetitive behaviors, and improve learning and memory in ASD animal models through inflammation regulation and apoptosis inhibition. The CaH NCs in managing and preventing ASD represents a paradigm shift in autism treatment, paving the alternative but efficient way for clinical interventions in neurological conditions.