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Updated: Aug 7, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
An engineered ferritin nanocage co-delivery system for targeted hair cells protection and hearing loss attenuation
Junying Zhang1,2, Zhiwei Zheng1, Jiaru Zhang3
1ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai, P. R. China.
Rationale:
Hearing loss is a common sensory disorder with few treatment options, mainly due to the blood-labyrinth barrier and lack of effective targeted delivery systems. Small molecules such as LLY283 and RG108 protect hair cells (HCs), but clinical use is limited by poor cellular uptake, off-target toxicity, and inefficient cochlear delivery.
Methods:
We developed a ferritin (Fn)-based nanocage (LR@Fn) to co-deliver RG108 and LLY283 via local injection through the round window membrane. Fn offers natural HC targeting, a hollow cavity, and good biocompatibility. Drugs were loaded using a pH-triggered strategy while maintaining structural and colloidal stability.
Results:
In neonatal cisplatin and adult noise-induced hearing loss models, LR@Fn reduced HCs loss, synaptic damage, and apoptosis more effectively than dexamethasone. LR@Fn treatment activated the Wnt/β-catenin pathway, which may contribute to the observed protective effect.
Conclusions:
LR@Fn is a biocompatible ferritin-based platform for targeted inner-ear therapy, showing potential for multiple forms of hearing loss.
