title: Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG-lipid nanoparticles.
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.
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou 310015, Zhejiang, China.
authors.forename: Ying-mei
authors.initials: YM
authors.lastname: Lu
authors.forename: Ji-yun
authors.initials: JY
authors.lastname: Huang
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Xue-fang
authors.initials: XF
authors.lastname: Lou
authors.forename: Mei-hua
authors.initials: MH
authors.lastname: Liao
authors.forename: Ling-juan
authors.initials: LJ
authors.lastname: Hong
authors.forename: Rong-rong
authors.initials: RR
authors.lastname: Tao
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Shan
authors.forename: Xiao-liang
authors.initials: XL
authors.lastname: Wang
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Yong-zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Feng
authors.initials: F
authors.lastname: Han
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry; D002545:Brain Ischemia / Q000628:therapy*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000276:immunology*; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000906:Antibodies; D053222:Fas Ligand Protein; D008055:Lipids; D011092:Polyethylene Glycols
keywords: 3-n-Butylphthalide; Brain ischaemia; Brain-targeted delivery; Fas ligand; PEGylated lipid nanoparticles