Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG-lipid nanoparticles

Ying mei Lu, Ji yun Huang, Huan Wang, Xue fang Lou, Mei hua Liao, Ling juan Hong, Rong rong Tao, Muhammad M. Ahmed, Chun lei Shan, Xiao liang Wang, Kohji Fukunaga, Yong zhong Du, Feng Han

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

The translation of experimental stroke research from the laboratory to successful clinical practice remains a formidable challenge. We previously reported that PEGylated-lipid nanoparticles (PLNs) effectively transport across the blood-brain barrier along with less inflammatory responses. In the present study, PLNs conjugated to Fas ligand antibody that selectively present on brain ischaemic region were used for therapeutic targeting. Fluorescent analysis of the mice brain show that encapsulated 3-n-Butylphthalide (dl-NBP) in PLNs conjugated with Fas ligand antibody effectively delivered to ipsilateral region of ischaemic brain. Furthermore, the confocal immunohistochemical study demonstrated that brain-targeted nanocontainers specifically accumulated on OX42 positive microglia cells in ischaemic region of mice model. Finally, dl-NBP encapsulated nano-drug delivery system is resulted in significant improvements in brain injury and in neurological deficit after ischaemia, with the significantly reduced dosages versus regular dl-NBP. Overall, these data suggests that PLNs conjugated to an antibody specific to the Fas ligand constituted an ideal brain targeting drug delivery system for brain ischaemia.

Original languageEnglish
Pages (from-to)530-537
Number of pages8
JournalBiomaterials
Volume35
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • 3-n-Butylphthalide
  • Brain ischaemia
  • Brain-targeted delivery
  • Fas ligand
  • PEGylated lipid nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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