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

• Published in: Biomaterials Vol. 35; no. 1; pp. 530 - 537
• Main Authors: Lu, Ying-mei, Huang, Ji-yun, Wang, Huan, Lou, Xue-fang, Liao, Mei-hua, Hong, Ling-juan, Tao, Rong-rong, Ahmed, Muhammad M, Shan, Chun-lei, Wang, Xiao-liang, Fukunaga, Kohji, Du, Yong-zhong, Han, Feng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2014
• Subjects: 3-n-Butylphthalide; Advanced Basic Science; Animals; Antibodies - administration & dosage; Antibodies - chemistry; Brain ischaemia; Brain Ischemia - therapy; Brain-targeted delivery; Dentistry; Disease Models, Animal; Fas ligand; Fas Ligand Protein - immunology; Lipids - chemistry; Mice; Nanoparticles; PEGylated lipid nanoparticles; Polyethylene Glycols - chemistry; PEGylated lipid nanoparticles; Fas ligand; Brain-targeted delivery; Brain ischaemia; 3-n-Butylphthalide
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.09.093

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.