Targeted drug delivery aims to enhance the biological availability of a chosen therapeutic agent while reducing adverse effects. The ability to target drugs to the spiral ganglion cells (SGCs) and cochlear nerve (CN) would create an advanced therapeutic strategy for the treatment of sensorineural hearing loss. Composed of US Food and Drug Administration (FDA)-approved medical materials, poly(
-poly(ethylene glycol) (PEG-b
-PCL) polymersomes (PMs) are efficiently taken up by the SGCs and spiral ganglion Schwann cells. This occurs without overt toxicity in vitro spiral ganglion cultures indicating that this type of nanoparticle holds promise for drug delivery to treat sensorineural hearing loss.1
Targetability of PMs to the neural element of the cochlea was achieved through ligand mediated multivalent binding to tyrosine kinase receptors and to p75 neurotrophin receptors.2
However, no in vivo studies on the targetability of functionalized PMs were reported and there is a risk that targeting tyrosine kinase receptors and p75 neurotrophin receptors may result in altered cell signalling, which in turn may affect the neural activity and viability of the SGCs.
An alternative approach to targeting SGCs and their processes might be achieved by using the Tet1 peptide (sequence H-L-N-I-L-S-T-L-W-K-Y-R), which was identified by phage display and showed a strong affinity to differentiated PC12 cells, primary motor neurons, and dorsal root ganglion cells. Tet1 peptide binds to the trisialoganglioside clostridial toxin (GT1b) receptors,3
which are also expressed in the cochlea.4
Any disruption in the neural activity and viability of SGCs might be avoided because GT1b is not involved in SGC cell signalling. Modification of nanoparticles with the Tet1 peptide has resulted in improved targeted gene delivery to neurons both in vitro and in vivo.6
We hypothesized that SGCs or CN targeted drug delivery could be achieved by using PEG-b
-PCL PMs functionalized with the Tet1 peptide.
In our previous study, unlabelled PMs that were delivered onto the round window membrane (RWM) did not appear in SGCs and spiral ganglion satellite cells.8
In the present study, PMs were functionalized with the Tet1 peptide. The targetability was evaluated using two therapeutic approaches in which the PMs were delivered via either transtympanic injection or cochleostomy. The inner ear distribution of Tet1 functionalized PMS (Tet1-PMS) was then assayed using confocal microscopy. Two different control samples of PMs, unlabelled PMs and PMs functionalized with a scrambled Tet1 sequence (ScrTet1), were used in this investigation.