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Reactive oxygen species contribute to NIHL pathogenesis by injuring the inner ear hair cells. Teriparatide (PTH1\u201034) exerts antioxidant properties in the context of osteoporosis. Thus, in the current study, a multifunctional thermosensitive nanodelivery system is developed, based on the unique anatomical structure of the inner ear, to load and sustain the release of PTH1\u201034 to alleviate hair cell damage. LR27\u2014a fusion peptide\u2014is assembled from a targeting peptide (A665) and cell\u2010penetrating peptide (Arg8) to target hair cells and increase the round window membrane permeability. In vitro, the antioxidant and anti\u2010apoptotic properties of the nanodelivery system are assessed after treating HEI\u2010OC1 cells and cochlear explants with hydrogen peroxide to simulate the oxidative environment. In vivo, injection of the nanodelivery system into the auditory bulb protects the hearing and hair cells of an NIHL mouse model. These results demonstrate the synergistic effects of multiple peptides in treating NIHL and their potential clinical applications.<\/jats:p>","DOI":"10.1002\/advs.202408798","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T02:08:07Z","timestamp":1739239687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Multifunctional Nanodelivery System Modified by Fusion Peptides Acts as Teriparatide Carrier for Noise\u2010Induced Hearing Loss Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Jiawen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuowen","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangzi","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihui","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine the Medical University of South Carolina  Charleston 29425 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyu","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6973-5449","authenticated-orcid":false,"given":"Zuhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00053.2017"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.02.022"},{"key":"e_1_2_9_2_1","volume":"9","author":"Ferguson M. 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