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.
Department of Otolaryngology, Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria.
Soumen
S
Roy
Alex H
AH
Johnston
Tracey A
TA
Newman
Rudolf
R
Glueckert
Jozsef
J
Dudas
Mario
M
Bitsche
Elisa
E
Corbacella
Gunde
G
Rieger
Alessandro
A
Martini
Anneliese
A
Schrott-Fischer
D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D007758:Ear, Inner / Q000033:anatomy & histology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry
D010446:Peptide Fragments; D020932:Nerve Growth Factor