Is oval window transport a royal gate for nanoparticle delivery to vestibule in the inner ear?
Is oval window transport a royal gate for nanoparticle delivery to vestibule in the inner ear?
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卵圆窗运输是纳米粒子输送到内耳前庭的皇家大门吗？
DOI：
10.1016/j.ejps.2018.02.031
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Ding, Shan;Xie, Shibao;Chen, Gang
通过纳米医学策略将药物递送到内耳已经成为管理包括听力和平衡障碍在内的内耳疾病的有效治疗方法。物质从中耳经圆窗膜（RWM）进入外淋巴液已被广泛接受，但经卵圆窗（OW）进入外淋巴液的通道长期被忽视。到目前为止，研究人员仍然对纳米颗粒（NPs）进入内耳的途径以及它们在局部应用后如何到达内耳知之甚少。在此，我们设计了荧光可追踪的壳聚糖（CS）NPs，研究了NP在耳蜗和前庭器官内的分布，并评估了NP转运的RWM和OW途径的可用性。有趣的是，在前庭毛细胞、暗细胞和支持细胞中有高水平的CS NPs，但在耳蜗毛细胞和上皮细胞中可以忽略不计。然而，在两种细胞模型L929和HEI-OC 1细胞系中以及在体外共孵育后的耳蜗外植体的毛细胞中，NP是可见的。这些综合研究表明，CS NPs可能直接通过OW进入前庭，然后优先在前庭器官细胞中积累。因此，进行了体内研究，并清楚地表明，CS纳米颗粒通过RWM和OW进入内耳，但后者在将纳米颗粒递送到前庭中起着主导作用，在镫骨底板的薄骨中具有生动的荧光信号。总体而言，这些研究结果首次表明，OW，作为一个皇家大门，提供了一个方便的访问，以促进CS NPs运输到内耳，铸造一个新的光在未来的临床应用的NPs在有效治疗前庭疾病，通过最大限度地减少与耳蜗毛细胞病理学相关的听力损失的风险。
Drug delivery to the inner ear by nanomedicine strategies has emerged as an effective therapeutic approach for the management of inner ear diseases including hearing and balance disorders. It is well accepted that substance enters the perilymph from the middle ear through the round window membrane (RWM), but the passage through the oval window (OW) has long been neglected. Up to now, researchers still know little about the pathway via which nanoparticles (NPs) enter the inner ear or how they reach the inner ear following local applications. Herein, we engineered fluorescence traceable chitosan (CS) NPs, investigated the NP distribution within cochlear and vestibular organs, and assessed the availability of RWM and OW pathways to NP transport. Intriguingly, there were high levels of CS NPs in vestibular hair cells, dark cells and supporting cells, but negligible ones in cochlear hair cells and epithelial cells after intratympanic administration. However, the NPs were visualized in two cell models, L929 and HEI-OC1 cell lines, and in the hair cells of cochlear explants after co-incubation in vitro. These combined studies implied that CS NPs might enter the vestibule directly through the OW and then preferentially accumulated in the cells of vestibular organs. Thus, in vivo studies were carried out and clearly revealed that CS NPs entered the inner ear through both the RWM and OW, but the latter played a governing role in delivering NPs to the vestibule with vivid fluorescence signals in the thin bone of the stapes footplate. Overall, these findings firstly suggested that the OW, as a royal gate, afforded a convenient access to facilitate CS NPs transport into inner ear, casting a new light on future clinical applications of NPs in the effective treatment of vestibular disorders by minimizing the risk of hearing loss associated with cochlear hair cell pathology.