A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

Xueling Wang,1–3,* Yuming Chen,1–3,* Yong Tao,1–3 Yunge Gao,1–3 Dehong Yu,1–3 Hao Wu1–3 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shan...

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Autores principales: Wang XL, Chen YM, Tao Y, Gao YG, Yu DH, Wu H
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:b2923a63c49e4e12a60c031902ce802b2021-12-02T07:35:17ZA666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss1178-2013https://doaj.org/article/b2923a63c49e4e12a60c031902ce802b2018-11-01T00:00:00Zhttps://www.dovepress.com/a666-conjugated-nanoparticles-target-prestin-of-outer-hair-cells-preve-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xueling Wang,1–3,* Yuming Chen,1–3,* Yong Tao,1–3 Yunge Gao,1–3 Dehong Yu,1–3 Hao Wu1–3 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The delivery of treatment agents to inner ear with drug delivery system (DDS) has been under investigation to overcome the limitations of the conventional therapeutic agents in curing or alleviating the cisplatin ototoxicity.Methods: In the present study, a novel targeted dexamethasone (DEX)-loaded DDS, A666-DEX-NP, was constructed for prevention from cisplatin-induced hearing loss. A666-(CLEPRWGFGWWLH) peptides specifically bind to prestin, which is limited to the outer hair cells (OHCs). HEI-OC1 and cisplatin-treated guinea pigs (12 mg/kg, intraperitoneal) were used as in vitro and in vivo models for investigating the targeting and protective efficiency against cisplatin.Results: As expected, compared to A666-unconjugated nanoparticles (NP), A666-conjugated coumarin 6-labeled NP showed active targeting to OHCs. Furthermore, A666-coumarin 6-labeled NP could be significantly internalized by HEI-OC1 cells via the A666–prestin interaction. This facilitated the uptake of cells pretreated with A666-DEX-NP, followed by the cisplatin-treated group, which led to enhanced cell viability, reduced apoptotic properties, and decreased reactive oxygen species levels as compared to cells pretreated with DEX or DEX-NP, 4 hours in advance of cisplatin treatment. In cisplatin-treated guinea pigs, pretreatment with A666-DEX-NP effectively preserved OHCs and showed significant hearing protection at 4, 8, and 16 kHz as compared to pretreatment with saline, DEX, or DEX-NP formulation.Conclusion: This OHC-targeting DDS provides a novel strategy for DEX application that can be potentially used to combat cisplatin ototoxicity. Keywords: A666 peptide, dexamethasone, prestin, cisplatin ototoxicity Wang XLChen YMTao YGao YGYu DHWu HDove Medical PressarticleA666 peptidedexamethasoneprestincisplatin ototoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7517-7531 (2018)
institution DOAJ
collection DOAJ
language EN
topic A666 peptide
dexamethasone
prestin
cisplatin ototoxicity
Medicine (General)
R5-920
spellingShingle A666 peptide
dexamethasone
prestin
cisplatin ototoxicity
Medicine (General)
R5-920
Wang XL
Chen YM
Tao Y
Gao YG
Yu DH
Wu H
A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
description Xueling Wang,1–3,* Yuming Chen,1–3,* Yong Tao,1–3 Yunge Gao,1–3 Dehong Yu,1–3 Hao Wu1–3 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The delivery of treatment agents to inner ear with drug delivery system (DDS) has been under investigation to overcome the limitations of the conventional therapeutic agents in curing or alleviating the cisplatin ototoxicity.Methods: In the present study, a novel targeted dexamethasone (DEX)-loaded DDS, A666-DEX-NP, was constructed for prevention from cisplatin-induced hearing loss. A666-(CLEPRWGFGWWLH) peptides specifically bind to prestin, which is limited to the outer hair cells (OHCs). HEI-OC1 and cisplatin-treated guinea pigs (12 mg/kg, intraperitoneal) were used as in vitro and in vivo models for investigating the targeting and protective efficiency against cisplatin.Results: As expected, compared to A666-unconjugated nanoparticles (NP), A666-conjugated coumarin 6-labeled NP showed active targeting to OHCs. Furthermore, A666-coumarin 6-labeled NP could be significantly internalized by HEI-OC1 cells via the A666–prestin interaction. This facilitated the uptake of cells pretreated with A666-DEX-NP, followed by the cisplatin-treated group, which led to enhanced cell viability, reduced apoptotic properties, and decreased reactive oxygen species levels as compared to cells pretreated with DEX or DEX-NP, 4 hours in advance of cisplatin treatment. In cisplatin-treated guinea pigs, pretreatment with A666-DEX-NP effectively preserved OHCs and showed significant hearing protection at 4, 8, and 16 kHz as compared to pretreatment with saline, DEX, or DEX-NP formulation.Conclusion: This OHC-targeting DDS provides a novel strategy for DEX application that can be potentially used to combat cisplatin ototoxicity. Keywords: A666 peptide, dexamethasone, prestin, cisplatin ototoxicity 
format article
author Wang XL
Chen YM
Tao Y
Gao YG
Yu DH
Wu H
author_facet Wang XL
Chen YM
Tao Y
Gao YG
Yu DH
Wu H
author_sort Wang XL
title A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
title_short A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
title_full A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
title_fullStr A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
title_full_unstemmed A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
title_sort a666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/b2923a63c49e4e12a60c031902ce802b
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