2. Academic Validation
  3. A OHCs-Targeted Strategy for PEDF Delivery in Noise-Induced Hearing Loss

A OHCs-Targeted Strategy for PEDF Delivery in Noise-Induced Hearing Loss

  • Adv Healthc Mater. 2025 Jan 26:e2403537. doi: 10.1002/adhm.202403537.
Zeqi Zhao 1 2 3,  Zhengzhong Han 4,  Yudi Shao 1 2 5,  Konduru Naveena 1 2 3,  Jintao Yuan 1 2 5,  Nan Zhou 1 2 5,  Caiji Wang 1 2 3,  Xuanyi Li 1 2 3,  Xi Shi 2 6 7,  Dan Jin 1 2 3,  Bing Xu 1 2 3,  Fuxing Dong 8,  Zhiwei Liu 8,  Wei Li 1 2 3,  Hongmei Liu 9,  Yuehua Qiao 1 2 3
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, P. R. China.
  • 2 Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou, 221002, P. R. China.
  • 3 Institute of Audiology and Balance Science, Xuzhou Medical University, Xuzhou, 221002, P. R. China.
  • 4 Department of Neurosurgery, Xuzhou Children's Hospital, Xuzhou, 221002, P. R. China.
  • 5 Central Laboratory, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, P. R. China.
  • 6 Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Hainan, 570228, P. R. China.
  • 7 Song Li's Academician Workstation of Hainan University, School of Pharmaceutical Sciences, Hainan, 572000, P. R. China.
  • 8 Public Experimental Research Center, Xuzhou Medical University, Xuzhou, 221002, P. R. China.
  • 9 Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China.
PMID: 39865717 DOI: 10.1002/adhm.202403537
Abstract

Noise-induced hearing loss (NIHL) results from prolonged exposure to intense noise, causing damage to sensory outer hair cells (OHCs) and spiral ganglion neurons (SGNs). The blood labyrinth barrier (BLB) hinders systemic drug delivery to the inner ear. This study applied a retro-auricular round window membrane (RWM) method to bypass the BLB, enabling the transport of macromolecular proteins into the inner ear. Pigment epithelium-derived factor (PEDF), which has anti-inflammatory and neuroprotective properties, is conjugated to a prestin-targeting peptide 2 (PrTP2) using N-succinimidyl-3-maleimidopropionate (SMP) to form PrTP2-SMP/PEDF. This compound specifically targeted Prestin and accumulated around OHCs for sustained release, effectively reducing OHC and SGN loss. Functional and structural tests, including auditory brainstem response (ABR), confocal microscopy, and scanning electron microscopy (SEM), revealed significant hearing restoration and cellular protection. Additionally, the results of enzyme-linked immunosorbent assay (ELISA), Annexin V and propidium iodide (PI) staining and immunoblotting show that noise exposure may induce Pyroptosis in the cochlea by activating the NOD-like Receptor protein 3 (NLRP3)-apoptosis-associated speck-like protein containing a CARD (ASC) - cysteinyl aspartate specific proteinase (Caspase-1) pathway and PrTP2-SMP/PEDF alleviates the inflammatory response by inhibiting Pyroptosis. Toxicity analysis indicates no adverse effects, suggesting that PrTP2-SMP/PEDF has a promising therapeutic prospective for NIHL.

Keywords

drug delivery; noise‐induced hearing loss; outer hair cells; pigment epithelium‐derived factor; spiral ganglion neurons.

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