PMID- 29109483
OWN - NLM
STAT- MEDLINE
DCOM- 20190806
LR  - 20220408
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 6
TI  - Safety of Nonporous Silica Nanoparticles in Human Corneal Endothelial Cells.
PG  - 14566
LID - 10.1038/s41598-017-15247-2 [doi]
LID - 14566
AB  - Nonporous silica nanoparticles (SiNPs) are promising drug carrier platforms for 
      intraocular drug delivery. In this study, we investigated the safety of three 
      different sizes of SiNPs (50, 100, and 150 nm) in a human corneal endothelial 
      cell (HCEC) line, B4G12. The HCECs were exposed to different concentrations (0, 
      25, 50, and 100 microg/ml) of three sizes of SiNPs for up to 48 h. Cellular 
      viability, autophagy, lactate dehydrogenase (LDH) assay, and mammalian target of 
      rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of 
      the SiNPs was evaluated with transmission electron microscopy (TEM). TEM revealed 
      that the SiNPs were up-taken by the HCECs inside cytoplasmic vacuoles. No 
      mitochondrial structural damage was observed. Both cellular viability and LDH 
      level remained unchanged with up to 100 microg/mL of SiNP treatment. Autophagy showed 
      a significant dose-dependent activation with 50, 100, and 150 nm SiNPs. However, 
      the mTOR activation remained unchanged. Human corneal tissue culture with 
      100 microg/ml concentrations of SiNPs for 72 h revealed no significant endothelial 
      toxicity. In vivo corneal safety of the SiNPs (0.05 ml intracameral injection, 
      200 mg/ml concentration) was also verified in rabbit models. These findings 
      suggested that 50, 100, and 150 nm SiNPs did not induce acute significant 
      cytotoxicity in corneal endothelial cells at concentrations up to 100 microg/mL. 
      However, long-term toxicity of SiNPs remains unknown.
FAU - Kim, Ja-Yeon
AU  - Kim JY
AUID- ORCID: 0000-0001-7605-0053
AD  - Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South 
      Korea.
FAU - Park, Joo-Hee
AU  - Park JH
AUID- ORCID: 0000-0002-8662-6279
AD  - Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South 
      Korea.
FAU - Kim, Martha
AU  - Kim M
AD  - Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South 
      Korea.
FAU - Jeong, Hyejoong
AU  - Jeong H
AD  - School of Chemical Engineering and Material Science, Chung-Ang University, Seoul, 
      South Korea.
FAU - Hong, Jinkee
AU  - Hong J
AD  - School of Chemical Engineering and Material Science, Chung-Ang University, Seoul, 
      South Korea.
FAU - Chuck, Roy S
AU  - Chuck RS
AD  - Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, 
      Albert Einstein College of Medicine, Bronx, NY, USA.
FAU - Park, Choul Yong
AU  - Park CY
AD  - Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South 
      Korea. oph0112@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171106
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 7631-86-9 (Silicon Dioxide)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
MH  - Autophagy/drug effects
MH  - Cell Survival/drug effects
MH  - Corneal Endothelial Cell Loss/*chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects
MH  - Endothelium, Corneal/*drug effects/ultrastructure
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Middle Aged
MH  - Nanoparticles/administration & dosage/*adverse effects
MH  - Silicon Dioxide/administration & dosage/*adverse effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5674045
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/08 06:00
MHDA- 2019/08/07 06:00
PMCR- 2017/11/06
CRDT- 2017/11/08 06:00
PHST- 2017/05/04 00:00 [received]
PHST- 2017/10/24 00:00 [accepted]
PHST- 2017/11/08 06:00 [entrez]
PHST- 2017/11/08 06:00 [pubmed]
PHST- 2019/08/07 06:00 [medline]
PHST- 2017/11/06 00:00 [pmc-release]
AID - 10.1038/s41598-017-15247-2 [pii]
AID - 15247 [pii]
AID - 10.1038/s41598-017-15247-2 [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 6;7(1):14566. doi: 10.1038/s41598-017-15247-2.