Amifostine-Loaded Nanocarrier Traverses the Blood–Brain Barrier and Prevents Radiation-Induced Brain Injury

作者：Xiaohui Zhao, Jinping Cheng, Shushu Gui, Meng Jiang, Dawei Qi, Jianghua Huang, Liren Fu, Shijie Liu, Yujia Ma, Juntian Shi, Zairui Wang, Weike Zeng, Xiumei Li, Kejia Liu, Yamei Tang · 发表于：ACS Applied Materials & Interfaces · 年份：2023 · DOI：10.1021/acsami.3c00502 · 被引用次数：26 · 研究领域：Effects of Radiation Exposure、Ultrasound and Hyperthermia Applications、Anesthesia and Neurotoxicity Research

Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors, and there is no satisfying prevention and effective treatment available for these patients. Amifostine (AMF) is a well-known free radical scavenger with demonstrated effectiveness in preventing radiation-induced toxicity. However, the limited permeability of AMF across the blood–brain barrier (BBB) when administered intravenously reduces the effectiveness of AMF in preventing RIBI. Herein, we construct a nanoparticle (NP) platform for BBB delivery of AMF. AMF is conjugated with 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine- n -[poly(ethylene glycol)]-hydroxy succinamide [DSPE-PEG-NHS, PEG M 2000], and the product is DSPE-PEG-AMF. Then, the nanoparticles (DAPP NPs) were formed by self-assembly of poly(lactic- co -glycolic acid) (PLGA), DSPE-PEG-AMF, and polysorbate 80 (PS 80). PEG shields the nanoparticles from blood clearance by the reticuloendothelial system and lengthens the drug circulation time. PS 80 is used to encapsulate nanoparticles for medication delivery to the brain. The results of our study showed that DAPP NPs were able to effectively penetrate the blood–brain barrier (BBB) in healthy C57BL/6 mice. Furthermore, in a well-established mouse model of X-knife-induced brain injury, treatment with DAPP NPs (corresponding to 250 mg/kg AMF) was found to significantly reduce the volume of brain necrosis c...