Multifunctional Self‐Assembling Peptide System for Preventing Noise‐Induced Hearing Loss

Functional self-assembling peptides prepared by linking short functional peptides to basic self-assembling peptides via solid-phase synthesis are often single-function and insufficient for preventing complex diseases, including noise-induced hearing loss (NIHL). Herein, a strategy to design multifunctional self‑assembling peptides (NPR36) for preventing NIHL is presented. Compared to the conventional approach of constructing multifunctional self-assembling peptide systems through co-assembling distinct functional peptides, this strategy integrates multiple functions into a single self-assembling peptide by conjugating multifunctional hormone-derived peptides with extended basic self-assembling peptides. This monolithic integration eliminates the need to balance concentration ratios and prevents efficacy loss that occurs when the concentration of any component drops below its therapeutic threshold, while also ensuring that each peptide possesses complete multifunctionality, thereby enhancing therapeutic effects. Benefiting from the non-covalent interactions of the extended assembly motif, NPR36 self‑assembling peptides can form nanofibers and achieve sustained release during disassembly, maintaining an effective concentration at the treatment site. Furthermore, a fiber-microalgae complex was formed by combining NPR36 with Spirulina platensis. This fiber-microalgae-based system synergistically exerted antioxidant and anti-apoptotic effects, markedly reducing hair cell loss and restoring hearing. Overall, preventive interventions based on multifunctional self-assembling peptides could overcome the clinical translation challenges in the prevention of inner ear disorders.