Neuromelanin-inspired metal-selenomelanin nanonetworks restore neuronal excitability in radiation-induced brain injury

Radiation-induced brain injury (RIBI) affects up to 30% of patients receiving cranial radiotherapy, representing an irreversible complication lacking effective therapies. Research advances are limited by poor blood-brain barrier drug penetration and overreliance on ex vivo pathology, which cannot resolve dynamic neuronal dysfunction. Inspired by neuromelanin, we fabricated metal-selenomelanin nanonetworks (MSMNs), combined with in vivo electrophysiology to investigate and mitigate radiation-triggered neural dysfunction. In 6-gray whole body–irradiated mice, MSMN normalized neuronal excitability and restored medium spiny neuron firing and striatal circuit activity, improving locomotor and anxiety-related behaviors. Besides central functional recovery, MSMN provides systemic radioprotection, ensuring full 30-day survival, protecting radiosensitive organs and facilitating hematopoietic recovery. This work identifies neuronal excitability as an underexplored therapeutic target for RIBI, establishing neuromelanin-mimetic selenomelanin nanonetworks as a bioinspired platform linking molecular radioprotection to circuit-level restoration for radiation-induced neurological injury.