Internalization of nanoparticles into spiral ganglion cells

Abstract

The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments
for conditions such as Ménière’s disease, tinnitus, schwannomas of the ear, and for improving hearing.
The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new
approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery
can be achieved by functionally “addressed” nanostructures loaded with a therapeutic molecule. In the present
study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles
(NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann
dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video
microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry
for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied
in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently
(Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using
fluorescence microscopy. The study demonstrates that DiI-loaded NPs can be internalized into guinea pig SG
neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced
viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the
cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in
axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small
vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead
to the development of more specialized NPs, targeting only SG neurons or Schwann cells.

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Identifiers

ORCID for T.A. Newman: orcid.org/0000-0002-3727-9258

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