An engineered ferritin nanocage co-delivery system for targeted hair cells protection and hearing loss attenuation.

IF 14.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Theranostics Pub Date : 2026-07-13 eCollection Date: 2026-01-01 DOI:10.7150/thno.131600

Junying Zhang, Zhiwei Zheng, Jiaru Zhang, Xinyuan Ma, Zihao Li, Hongyan Lin, Guohui Nie, Minmin Liang, Hui Ding, Yingzi He

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引用次数: 0

Abstract

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.

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一种针对毛细胞保护和听力损失衰减的工程铁蛋白纳米笼共递送系统。

理由：听力损失是一种常见的感觉障碍，治疗选择很少，主要是由于血液迷宫屏障和缺乏有效的靶向输送系统。小分子如LLY283和RG108保护毛细胞（hc），但由于细胞摄取不良、脱靶毒性和低效率的耳蜗传递，临床应用受到限制。方法：制备了一种基于铁蛋白（Fn）的纳米笼（LR@Fn），通过圆窗膜局部注射，将RG108和LLY283共同递送。Fn具有天然的HC靶向性、中空腔和良好的生物相容性。在保持结构和胶体稳定性的同时，使用ph触发策略装载药物。结果：在新生儿顺铂和成人噪声性听力损失模型中，LR@Fn比地塞米松更有效地减少了hc损失、突触损伤和细胞凋亡。LR@Fn处理激活了Wnt/β-catenin通路，这可能有助于观察到的保护作用。结论：LR@Fn是一种基于铁蛋白的生物相容性内耳治疗平台，具有治疗多种形式听力损失的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

25.40

自引率

1.60%

发文量

433

审稿时长

1 months

期刊介绍： Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.