Microalgae-MOF integrated drug delivery system for cranial radiotherapy and chemotherapy-induced brain injury

The combination of cranial radiotherapy and chemotherapy may cause brain damage and cognitive dysfunction, therefore developing protective strategies for the treatment of chemoradiotherapy-induced brain injury is of great significance. Deferoxamine is an efficient iron chelator to inhibit ferroptosis which induced by radiotherapy and chemotherapy, but it has low oral bioavailability and difficulty in crossing the blood brain barrier (BBB), which limit its clinical translation. Herein, we constructed an orally microalgae-metal-organic framework (MOF) integrated drug delivery system (DFO@MOF@SP) for the protection of chemoradiotherapy-induced ferroptosis-related brain injury. Spirulina platensis (SP) can improve the biodistribution of nano-drugs in the intestines and enhance their oral bioavailability. The MOF nanoparticles as vectors for the delivery of deferoxamine (DFO), and modified by Angiopep-2 to improve their ability to cross the BBB (DFO@MOF). The in vitro and in vivo experimental results displayed that DFO@MOF@SP system has high safety and can exert good neuroprotective effect. We confirmed that DFO@MOF@SP system could improve the cognitive function and alleviate neurogenesis impairment and glial activation in mice subjected to chemoradiotherapy, and its neuroprotective mechanisms mainly include inhibiting ferroptosis and regulating gut microbiota. This study can provide new direction for the treatment of brain injury in patients undergoing cranial radiotherapy and chemotherapy.