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Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery

Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery
Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery
Cell specific targeting is an emerging field in nanomedicine. Homing of the multifunctional nanoparticles (MFNPs) is achieved by the conjugation of targeting moieties on the nanoparticle surface. The inner ear is an attractive target for new drug delivery strategies as it is hard to access and hearing loss is a significant worldwide problem. In this work we investigated the utility of a Nerve Growth Factor-derived peptide (hNgf_EE) functionalized nanoparticles (NPs) to target cells of the inner ear. These functionalized NPs were introduced to organotypic explant cultures of the mouse inner ear and to PC-12 rat pheochromocytoma cells. The NPs did not show any signs of toxicity. Specific targeting and higher binding affinity to spiral ganglion neurons, Schwann cells and nerve fibers of the explant cultures were achieved through ligand mediated multivalent binding to tyrosine kinase receptors and to p75 neurotrophin receptors. Unspecific uptake of NPs was investigated using NPs conjugated with scrambled hNgf_EE peptide. Our results indicate a selective cochlear cell targeting by MFNPs, which may be a potential tool for cell specific drug and gene delivery to the inner ear
inner ear, spiral ganglion neurons, nanoparticles, hearing loss
0378-5173
214-224
Roy, Soumen
25bd32b7-252d-47c4-9185-436fe23f5614
Johnston, Alex H.
3ae749e9-d566-4a4e-9e77-88ea3c22b470
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Glueckert, Rudolf
86983aec-7f03-4823-91ce-e19a5db97286
Dudas, Jozsef
ecb50614-59d9-44fb-9216-a5429c70f8db
Bitsche, Mario
a3dce341-33c1-44fd-86a8-d37b571ebe9a
Corbacella, Elisa
c19ea7ab-2e44-4ebb-a219-81dca4da5cba
Rieger, Gunde
f38490d9-2ec8-43aa-93bb-04ca74a173b9
Martini, Alessandro
e2215413-b45f-4322-852f-bfa2c2a6ec7b
Fischer, Anneliese Schrott
e8635b20-677d-46a1-9b75-8cf79e9e7a2c
Roy, Soumen
25bd32b7-252d-47c4-9185-436fe23f5614
Johnston, Alex H.
3ae749e9-d566-4a4e-9e77-88ea3c22b470
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Glueckert, Rudolf
86983aec-7f03-4823-91ce-e19a5db97286
Dudas, Jozsef
ecb50614-59d9-44fb-9216-a5429c70f8db
Bitsche, Mario
a3dce341-33c1-44fd-86a8-d37b571ebe9a
Corbacella, Elisa
c19ea7ab-2e44-4ebb-a219-81dca4da5cba
Rieger, Gunde
f38490d9-2ec8-43aa-93bb-04ca74a173b9
Martini, Alessandro
e2215413-b45f-4322-852f-bfa2c2a6ec7b
Fischer, Anneliese Schrott
e8635b20-677d-46a1-9b75-8cf79e9e7a2c

Roy, Soumen, Johnston, Alex H., Newman, Tracey A., Glueckert, Rudolf, Dudas, Jozsef, Bitsche, Mario, Corbacella, Elisa, Rieger, Gunde, Martini, Alessandro and Fischer, Anneliese Schrott (2010) Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery. International Journal of Pharmaceutics, 390 (2), 214-224. (doi:10.1016/j.ijpharm.2010.02.003). (PMID:20153412)

Record type: Article

Abstract

Cell specific targeting is an emerging field in nanomedicine. Homing of the multifunctional nanoparticles (MFNPs) is achieved by the conjugation of targeting moieties on the nanoparticle surface. The inner ear is an attractive target for new drug delivery strategies as it is hard to access and hearing loss is a significant worldwide problem. In this work we investigated the utility of a Nerve Growth Factor-derived peptide (hNgf_EE) functionalized nanoparticles (NPs) to target cells of the inner ear. These functionalized NPs were introduced to organotypic explant cultures of the mouse inner ear and to PC-12 rat pheochromocytoma cells. The NPs did not show any signs of toxicity. Specific targeting and higher binding affinity to spiral ganglion neurons, Schwann cells and nerve fibers of the explant cultures were achieved through ligand mediated multivalent binding to tyrosine kinase receptors and to p75 neurotrophin receptors. Unspecific uptake of NPs was investigated using NPs conjugated with scrambled hNgf_EE peptide. Our results indicate a selective cochlear cell targeting by MFNPs, which may be a potential tool for cell specific drug and gene delivery to the inner ear

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More information

Submitted date: 25 November 2009
Accepted/In Press date: 25 November 2009
Published date: 10 May 2010
Keywords: inner ear, spiral ganglion neurons, nanoparticles, hearing loss
Organisations: Biological Sciences, Clinical Neurosciences

Identifiers

Local EPrints ID: 72704
URI: http://eprints.soton.ac.uk/id/eprint/72704
ISSN: 0378-5173
PURE UUID: 2f05e11c-8b27-4564-9476-6c936eb856de
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

Catalogue record

Date deposited: 19 Feb 2010
Last modified: 14 Mar 2024 02:39

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Contributors

Author: Soumen Roy
Author: Alex H. Johnston
Author: Rudolf Glueckert
Author: Jozsef Dudas
Author: Mario Bitsche
Author: Elisa Corbacella
Author: Gunde Rieger
Author: Alessandro Martini
Author: Anneliese Schrott Fischer

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