Guo Tao, Wang Yuxin, Hayat Muhammad Abid, Si Yu, Ni Yining, Zhang Jingwen, Qiu Yun, Zeng Yu, Cao Yudie, Hong Yancheng, Chen Bo, Hu Jiabo
Institute of Cerebrovascular Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China; Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Int J Biol Macromol. 2025 Apr;302:140542. doi: 10.1016/j.ijbiomac.2025.140542. Epub 2025 Jan 31.
Intracerebral hemorrhage (ICH) is a severe form of stroke with high mortality and disability rates, largely due to its complex pathology. Currently, no effective therapies exist. Rosuvastatin has shown neuroprotective effects, but its low bioavailability and poor targeting to hemorrhagic sites limit its therapeutic efficacy. To overcome these challenges, this study developed rosuvastatin-loaded human H-ferritin nanoparticles (Rsv@HFn) as a brain-targeting nanoplatform. This nanoplatform enhances the drug's ability to cross the blood-brain barrier, increasing its accumulation at the injury site and improves its therapeutic efficacy. Rsv@HFn also facilitates the translocation of Nrf-2 to the nucleus, increasing HO-1 and CD91 expression and promoting the shift of M1 microglia to the M2 phenotype and reducing neuroinflammation and oxidative stress. Additionally, Rsv@HFn improves blood-brain barrier integrity, reduced brain edema, and alleviated neuropathological damage in ICH mice. Overall, this study introduces a promising therapeutic strategy for ICH by improving drug delivery and targeting, reducing inflammation, and enhancing recovery. These findings provide new avenues for future clinical research in treating ICH.
脑出血（ICH）是一种严重的中风形式，死亡率和致残率很高，这主要归因于其复杂的病理过程。目前，尚无有效的治疗方法。瑞舒伐他汀已显示出神经保护作用，但其低生物利用度和对出血部位的靶向性差限制了其治疗效果。为了克服这些挑战，本研究开发了负载瑞舒伐他汀的人H-铁蛋白纳米颗粒（Rsv@HFn）作为一种脑靶向纳米平台。该纳米平台增强了药物穿越血脑屏障的能力，增加了其在损伤部位的蓄积，并提高了其治疗效果。Rsv@HFn还促进Nrf-2向细胞核的转位，增加HO-1和CD91的表达，并促进M1小胶质细胞向M2表型的转变，减轻神经炎症和氧化应激。此外，Rsv@HFn改善了血脑屏障的完整性，减轻了脑出血小鼠的脑水肿，并减轻了神经病理损伤。总体而言，本研究通过改善药物递送和靶向性、减轻炎症和促进恢复，为脑出血引入了一种有前景的治疗策略。这些发现为未来脑出血临床研究提供了新途径。
