Recent Advances in Functionalized Nanoparticles for Targeted and Controlled Inner Ear Therapy via Localized Cochlear Delivery

Treatment of sensorineural hearing loss (SNHL) is challenging due to the inner ear's complex anatomy and physiological barriers, such as the blood-labyrinth barrier. Nanoparticle-based drug delivery systems have emerged as promising solutions, offering targeted, sustained, and stimuli-responsive therapeutic options. This review discusses recent advancements in nanoparticle functionalization strategies for inner ear drug delivery. Active targeting approaches, such as the use of prestin-specific peptides, enable selective delivery to outer hair cells. Stimuli-responsive systems, including thermosensitive hydrogels and light-activated nanoparticles, facilitate controlled drug release in response to internal or external triggers. Surface modifications with polyethylene glycol, cell-penetrating peptides, and cationic charges enhance permeability across the round window membrane and improve cellular uptake. These functionalized nanoparticles have demonstrated improved cochlear targeting and therapeutic outcomes in preclinical models of SNHL. Continued development of these multifunctional, biocompatible systems holds considerable promise for clinical translation in the treatment of SNHL.