A Multifunctional Nanodelivery System Modified by Fusion Peptides Acts as Teriparatide Carrier for Noise-Induced Hearing Loss Therapy.

Abstract

Noise-induced hearing loss (NIHL) is among the most poorly treated diseases due to irreversible damage to hair cells. Reactive oxygen species contribute to NIHL pathogenesis by injuring the inner ear hair cells. Teriparatide (PTH1-34) 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 PTH1-34 to alleviate hair cell damage. LR27-a fusion peptide-is assembled from a targeting peptide (A665) and cell-penetrating peptide (Arg8) to target hair cells and increase the round window membrane permeability. In vitro, the antioxidant and anti-apoptotic properties of the nanodelivery system are assessed after treating HEI-OC1 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.