Metal-organic framework-edaravone nanoparticles for radiotherapy-induced brain injury treatment

Cranial radiotherapy may cause damage to normal brain tissues and induce cognitive dysfunction, so developing an effective strategy to prevent radiotherapy-induced brain injury is essential. Metal-organic frameworks (MOFs) can be used as vectors for the delivery of neuroprotective drugs due to their high drug loading capacity and low toxicity. In this study, we synthesized MIL-53(Cr) nanoparticles, which were used to deliver edaravone, and modified the surface of the nanoparticles with polyethylene glycol and Angiopep-2 (EDA@MIL-53(Cr)-P/A) to improve their oral bioavailability and ability to cross the blood-brain barrier (BBB). We confirmed that MIL-53(Cr)-P/A nanoparticles could achieve the sustained release of edaravone and enhance its ability to cross the BBB. The results of in vitro experiments showed that EDA@MIL-53(Cr)-P/A could exert radioprotective effects on HT22 and BV2 cells. We also demonstrated that EDA@MIL-53(Cr)-P/A could alleviate brain injury and cognitive dysfunction in mice receiving whole-brain irradiation. Mechanistically, EDA@MIL-53(Cr)-P/A alleviated irradiation-induced brain damage by inhibiting oxidative stress, DNA damage, apoptosis and inflammatory reactions. This study provides a new strategy for the protection against radiotherapy-induced brain injury.