Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear.
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 (A(665) and A(666)) 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 A(665) and A(666) 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.
Department of Otolaryngology, University of Tampere, Tampere, Finland. Elena.Surovtseva@uta.fi
Elena V
EV
Surovtseva
Alexander H
AH
Johnston
Weikai
W
Zhang
Ya
Y
Zhang
Adele
A
Kim
Michio
M
Murakoshi
Hiroshi
H
Wada
Tracey A
TA
Newman
Jing
J
Zou
Ilmari
I
Pyykkö
D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D003051:Cochlea / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D020409:Molecular Motor Proteins / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
D007783:Lactones; D008024:Ligands; D020409:Molecular Motor Proteins; D009842:Oligopeptides; C498720:Pres protein, mouse; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols