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World J Otorhinolaryngol. Nov 28, 2013; 3(4): 114-133
Published online Nov 28, 2013. doi: 10.5319/wjo.v3.i4.114
Nanoparticle based inner ear therapy
Ilmari Pyykkö, Jing Zou, Ya Zhang, Weikai Zhang, Hao Feng, Paavo Kinnunen
Ilmari Pyykkö, Jing Zou, Ya Zhang, Weikai Zhang, Hao Feng, Department of Otolaryngology, Hearing and Balance Research Unit, University Hospital of Tampere, 33520 Tampere, Finland
Ya Zhang, Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Weikai Zhang, Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Paavo Kinnunen, Department of Biomedical Engineering and Computational Science, Aalto University, 02150 Esbo, Finland
Author contributions: Pyykkö I, Zou J designed the research; Zhang Y, Zhang W, Feng H performed in vitro and in vivo experiments on selected nanoparticles; Kinnunen P designed and produced the lipoplexies; Zou J analyzed data; Pyykkö I wrote the paper.
Supported by EU Nanoear Integrated Project NMP4-CT-2006-026556; and EU NanoCI Collaborative Project FP7 281056
Correspondence to: Ilmari Pyykkö, Professor, Department of otolaryngology, Hearing and Balance Research Unit, University of Tampere, Teiskontie 35, M-building Room 318, 33520 Tampere, Finland. ilmari.pyykko@uta.fi
Telephone: +358-3-31166387 Fax: +358-3-31164366
Received: May 5, 2013
Revised: August 22, 2013
Accepted: October 17, 2013
Published online: November 28, 2013
Processing time: 211 Days and 22.9 Hours
Abstract

Synthetic nanoparticles can be used to carry drugs, genes, small interfering RNA (siRNA) and growth factors into the inner ear, to repair, restore and induce cellular regeneration. Nanoparticles (NPs) have been developed which are targetable to selected tissue, traceable in vivo, and equipped with controlled drug/gene release. The NPs are coated with a ‘stealth’ layer, and decorated with targeting ligands, markers, transfection agents and endosomal escape peptides. As payloads, genes such as the BDNF-gene, Math1-gene and Prestin-gene have been constructed and delivered in vitro. Short-hairpin RNA has been used in vitro to silence the negative regulator of Math1, the inhibitors of differentiation and DNA binding. In order to facilitate the passage of cargo from the middle ear to the inner ear, the oval window transports gadolinium chelate more efficiently than the round window and is the key element in introducing therapeutic agents into the vestibule and cochlea. Depending upon the type of NPs, different migration and cellular internalization pathways are employed, and optimal carriers should be designed depending on the cargo. The use of NPs as drug/gene/siRNA carriers is fascinating and can also be used as an intraoperative adjunct to cochlear implantation to attract the peripheral processes of the cochlear nerve.

Keywords: Synthetic vector; Gene delivery; shRNA delivery; Targeted cochlear therapy; Minimally invasive therapy

Core tip: Several novel, multifunctional nanoparticles have been developed, which are targetable to selected tissue, biodegradable, traceable in vivo, and equipped with controlled payload release. They can be used to transport therapeutic agents, such as drugs, genes, small interfering RNAs and growth factors into the inner ear. To visualise the targetability and accuracy of the delivery, the nanoparticles can be traced with magnetic resonance imaging. It is hoped that this technology will come to be used as an alternative carrier to viral vectors traditionally used in gene delivery, but without the severe adverse effect.