Praetorius Mark, Brunner Christian, Lehnert Bernhard, Klingmann Christoph, Schmidt Helmut, Staecker Hinrich, Schick Bernhard
Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg Medical Center, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Acta Otolaryngol. 2007 May;127(5):486-90. doi: 10.1080/00016480600895102.
Silica nanoparticles may serve as a nonviral delivery system to the sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular organ, as well as the cochlear nucleus.
At present there are no targeted therapeutics for inner ear disease. A variety of viral vector systems have been tested in the inner ear with variable efficacy but they are still not regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral method of delivering a variety of macromolecules that potentially can be used for delivery within the auditory system. In this study, we evaluated the distribution and safety of nanoparticles in the inner ear.
Cy3-labeled silica nanoparticles were placed on the round window membrane of adult mice. Hearing thresholds were determined after nanoparticle delivery by auditory brainstem responses (ABRs). Distribution of particles was determined by histological evaluation of the cochlea, vestibular organs, and brain stem.
Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in the sensory hair cells and the spiral ganglion neurons of both the treated and contralateral inner ears. Additionally, the distal part of the central auditory pathway (dorsal cochlear nucleus, superior olivary complex) was found to be labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal transport. No hearing loss or inflammation was noted in the treated cochlea.
二氧化硅纳米颗粒可作为一种非病毒递送系统，作用于感觉毛细胞、耳蜗内的螺旋神经节细胞、前庭器官以及耳蜗核。
目前尚无针对内耳疾病的靶向治疗方法。多种病毒载体系统已在内耳进行测试，疗效各异，但仍不被视为内耳递送的安全系统。纳米颗粒是递送多种大分子的非病毒方法，有可能用于听觉系统内的递送。在本研究中，我们评估了纳米颗粒在内耳中的分布及安全性。
将Cy3标记的二氧化硅纳米颗粒置于成年小鼠的圆窗膜上。通过听性脑干反应（ABR）测定纳米颗粒递送后的听力阈值。通过对耳蜗、前庭器官和脑干进行组织学评估来确定颗粒的分布。
荧光显微镜显示，在处理侧和对侧内耳的感觉毛细胞和螺旋神经节神经元中均有Cy3标记的纳米颗粒信号。此外，发现中枢听觉通路的远端部分（蜗背侧核、上橄榄复合体）被Cy3连接的二氧化硅纳米颗粒标记，表明存在逆行轴突运输。在处理的耳蜗中未观察到听力损失或炎症。
