Nanoengineered, ultrasmall and catalytic potassium calcium hexacyanoferrate for neuroprotection and temporal lobe epilepsy treatment.

Hippocampal sclerosis, characterized by significant hippocampal neuronal loss, oxidative stress, glial cell proliferation, and inflammatory responses, constitutes a pivotal component in the pathogenesis of temporal lobe epilepsy (TLE). Traditional treatment strategies, mainly involving anti-epileptic drugs, face challenges including ineffectiveness, drug tolerance, and adverse reactions, complicating management of the condition. Herein, we design and engineer ultrasmall potassium calcium hexacyanoferrate (III) nanoparticles, designated as KCaHNPs, which feature a broad spectrum of enzymatic activities analogous to superoxide dismutase, catalase, peroxidase, and glutathione peroxidase. KCaHNPs efficiently neutralize excessive reactive oxygen species, mitigate mitochondrial dysfunction, maintain neuronal integrity, and prevent apoptosis. Importantly, KCaHNPs significantly reduce neuronal damage, apoptosis, ferroptosis, and glial cells activation in TLE-afflicted rats, thereby improving spatial and short-term memory, and diminishing epileptic hyperexcitability. Prophylactic deployment of KCaHNPs markedly decreases the frequency and duration of seizures, extends the latency period before the onset of initial seizures, and enhances neural functions within the hippocampal CA3 area. Collectively, these findings underscore the potent therapeutic and prophylactic efficacy of KCaHNPs in mitigating TLE by bolstering cellular defense mechanisms against oxidative stress and inflammation. This innovative approach holds promise as a comprehensive and efficacious strategy for managing temporal lobe epilepsy and potentially other complex neurological disorders.