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Nanoparticle based inner ear therapy

World Journal of Otorhinolaryngology 2013年第4期3卷 114-133页

作者： Ilmari Pyykk Jing Zou Ya Zhang Weikai Zhang Hao Feng Paavo Kinnunen Department of Otolaryngology Hearing and Balance Research Unit University Hospital of Tampere 33520 Tampere Finland Department of Otolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Orthopedics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Biomedical Engineering and Computational Science Aalto University 02150 Esbo Finland

Synthetic nanoparticles can be used to carry drugs, genes, small interfering RNA （siRNA） and growth fac-tors 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 in-hibitors 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 effciently 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.

关键词： Synthetic vector Gene delivery shRNA delivery targeted cochlear therapy Minimally invasive therapy

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