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  2. Recombinant human heavy-chain ferritin nanoparticles loaded with rosuvastatin attenuates secondary brain injury in intracerebral hemorrhage

Recombinant human heavy-chain ferritin nanoparticles loaded with rosuvastatin attenuates secondary brain injury in intracerebral hemorrhage

  • Int J Biol Macromol. 2025 Apr:302:140542. doi: 10.1016/j.ijbiomac.2025.140542.
Tao Guo 1 Yuxin Wang 2 Muhammad Abid Hayat 3 Yu Si 4 Yining Ni 5 Jingwen Zhang 6 Yun Qiu 7 Yu Zeng 8 Yudie Cao 9 Yancheng Hong 10 Bo Chen 11 Jiabo Hu 12
Affiliations

Affiliations

  • 1 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. Electronic address: gt488332613@163.com.
  • 2 Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China. Electronic address: 18261965597@163.com.
  • 3 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. Electronic address: abid.hayat@uvas.edu.pk.
  • 4 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. Electronic address: sy15556939689@163.com.
  • 5 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. Electronic address: nyyvin@163.com.
  • 6 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. Electronic address: jwzdgzdcp@163.com.
  • 7 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. Electronic address: qy19980415@163.com.
  • 8 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. Electronic address: z2560779861@163.com.
  • 9 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. Electronic address: hilary200033@163.com.
  • 10 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. Electronic address: hongyancheng2001@163.com.
  • 11 Institute of Cerebrovascular Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China. Electronic address: chenbo-19771202@163.com.
  • 12 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; Zhenjiang Blood Center, Zhenjiang, Jiangsu 212013, China. Electronic address: hu@ujs.edu.cn.
Abstract

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.

Keywords

Blood-brain barrier; Intracerebral hemorrhage; Recombinant human ferritin nanoparticles; Rosuvastatin; Secondary brain injury.

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