Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear
Surovtesva, Elena V., Johnston, Alexander H., Zhang, Weikai, Zhang, Ya, Kim, Adele, Murakoshi, Michio, Wada, Hiroshi, Newman, Tracey A., Zou, Jing and Pyykko, Illmari (2011) Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear. International Journal of Pharmaceutics (doi:10.1016/j.ijpharm.2011.12.042). (PMID:22227343).
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Targeted delivery of treatment agents to the inner ear using nanoparticles is an advanced therapeutic approach to cure or alleviate hearing loss. Designed to target the outer hair cells of the cochlea, two 12-mer peptides (A665 and A666) with affinity to prestin were identified following 3 rounds of sequential phage display. Two-round display with immobilized prestin protein was used to enrich the library for full-length prestin. The last round was performed using Cos-7 cells transiently transfected with a cCFP-prestin plasmid to display phages expressing peptides restrictive to the extracellular loops of prestin. The binding properties of A665 and A666 shown by flow cytometry demonstrated selectivity to prestin-expressing Chinese hamster ovary cells. PEG6K-b-PCL19K polymersomes covalently labelled with these peptides demonstrated effective targeting to outer hair cells in a rat cochlear explant study.
|Digital Object Identifier (DOI):||doi:10.1016/j.ijpharm.2011.12.042|
|Subjects:||Q Science > QH Natural history > QH301 Biology
R Medicine > RS Pharmacy and materia medica
|Divisions:||Faculty of Medicine
|Date Deposited:||09 Jan 2012 16:52|
|Last Modified:||31 Mar 2016 13:48|
3g-Nanotechnology based targeted drug delivery using the inner ear as a model target organ (NANOEAR)
Funded by: European Commission - FP6 (26556)
1 November 2006 to 31 October 2011
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