Transsynaptic delivery of nanoparticles to the central auditory nervous system.
CONCLUSIONS
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.
Praetorius
Mark
M
Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg Medical Center, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. mark.praetorius@med.uni-heidelberg.de
Brunner
Christian
C
Lehnert
Bernhard
B
Klingmann
Christoph
C
Schmidt
Helmut
H
Staecker
Hinrich
H
Schick
Bernhard
B
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D001370:Axonal Transport / Q000502:physiology; D017626:Cochlear Nucleus / Q000378:metabolism; D004292:Dominance, Cerebral / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006198:Hair Cells, Auditory / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000378:metabolism; D009847:Olivary Nucleus / Q000378:metabolism; D012405:Round Window, Ear / Q000378:metabolism*; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013136:Spiral Ganglion / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D014725:Vestibular Nerve / Q000378:metabolism
D012822:Silicon Dioxide