PMID- 29584754
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181114
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 3
DP  - 2018
TI  - Long-term delivery of brain-derived neurotrophic factor (BDNF) from nanoporous 
      silica nanoparticles improves the survival of spiral ganglion neurons in vitro.
PG  - e0194778
LID - 10.1371/journal.pone.0194778 [doi]
LID - e0194778
AB  - Sensorineural hearing loss (SNHL) can be overcome by electrical stimulation of 
      spiral ganglion neurons (SGNs) via a cochlear implant (CI). Restricted CI 
      performance results from the spatial gap between the SGNs and the electrode, but 
      the efficacy of CI is also limited by the degeneration of SGNs as one consequence 
      of SHNL. In the healthy cochlea, the survival of SGNs is assured by endogenous 
      neurotrophic support. Several applications of exogenous neurotrophic supply have 
      been shown to reduce SGN degeneration in vitro and in vivo. In the present study, 
      nanoporous silica nanoparticles (NPSNPs), with an approximate diameter of <100 
      nm, were loaded with the brain-derived neurotrophic factor (BDNF) to test their 
      efficacy as long-term delivery system for neurotrophins. The neurotrophic factor 
      was released constantly from the NPSNPs over a release period of 80 days when the 
      surface of the nanoparticles had been modified with amino groups. Cell culture 
      investigations with NIH3T3 fibroblasts attest a good general cytocompatibility of 
      the NPSNPs. In vitro experiments with SGNs indicate a significantly higher 
      survival rate of SGNs in cell cultures that contained BDNF-loaded nanoparticles 
      compared to the control culture with unloaded NPSNPs (p<0.001). Importantly, also 
      the amounts of BDNF released up to a time period of 39 days increased the 
      survival rate of SGNs. Thus, NPSNPs carrying BDNF are suitable for the treatment 
      of inner ear disease and for the protection and the support of SGNs. Their 
      nanoscale nature and the fact that a direct contact of the nanoparticles and the 
      SGNs is not necessary for neuroprotective effects, should allow for the facile 
      preparation of nanocomposites, e.g., with biocompatible polymers, to install 
      coatings on implants for the realization of implant-based growth factor delivery 
      systems.
FAU - Schmidt, Nadeschda
AU  - Schmidt N
AUID- ORCID: 0000-0002-6516-4562
AD  - Institut fur Anorganische Chemie, Leibniz Universitat Hannover, Hannover, 
      Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
FAU - Schulze, Jennifer
AU  - Schulze J
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical 
      School, Hannover, Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
FAU - Warwas, Dawid P
AU  - Warwas DP
AD  - Institut fur Anorganische Chemie, Leibniz Universitat Hannover, Hannover, 
      Germany.
FAU - Ehlert, Nina
AU  - Ehlert N
AD  - Institut fur Anorganische Chemie, Leibniz Universitat Hannover, Hannover, 
      Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
FAU - Lenarz, Thomas
AU  - Lenarz T
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical 
      School, Hannover, Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
FAU - Warnecke, Athanasia
AU  - Warnecke A
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical 
      School, Hannover, Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
FAU - Behrens, Peter
AU  - Behrens P
AD  - Institut fur Anorganische Chemie, Leibniz Universitat Hannover, Hannover, 
      Germany.
AD  - Cluster of Excellence Hearing4all, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180327
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Immobilized Proteins)
RN  - 7631-86-9 (Silicon Dioxide)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/chemistry/metabolism/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Drug Liberation
MH  - Immobilized Proteins/chemistry/pharmacology
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - NIH 3T3 Cells
MH  - Nanoparticles/*chemistry
MH  - Nanopores
MH  - Neurites/physiology
MH  - Particle Size
MH  - Rats
MH  - Silicon Dioxide/*chemistry
MH  - Spiral Ganglion/cytology/drug effects/metabolism
PMC - PMC5870973
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/03/28 06:00
MHDA- 2018/07/10 06:00
PMCR- 2018/03/27
CRDT- 2018/03/28 06:00
PHST- 2017/11/17 00:00 [received]
PHST- 2018/03/11 00:00 [accepted]
PHST- 2018/03/28 06:00 [entrez]
PHST- 2018/03/28 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2018/03/27 00:00 [pmc-release]
AID - PONE-D-17-40735 [pii]
AID - 10.1371/journal.pone.0194778 [doi]
PST - epublish
SO  - PLoS One. 2018 Mar 27;13(3):e0194778. doi: 10.1371/journal.pone.0194778. 
      eCollection 2018.