The effects of nonporous silica nanoparticles on cultured human keratocytes

Bora Yim, Joo Hee Park, Hyejoong Jeong, Jinkee Hong, Young Joo Shin, Roy S. Chuck, Choul Yong Park

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE. Silica nanoparticles (SiNPs) are promising carriers for ophthalmic drug delivery. In this study, we investigated the effect of various sizes of nonporous SiNPs on cultured human keratocytes. METHODS. Three different sizes of SiNPs (50, 100, and 150 nm) were manufactured. Primarily cultured human keratocytes were exposed to different concentrations (0, 25, 50, and 100 μg/ mL) of three sizes of SiNPs for up to 72 hours. Intracellular reactive oxygen species (ROS) generation, cellular viability, lactate dehydrogenase (LDH) assay, autophagy, vimentin expression, and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of SiNPs was evaluated with transmission electron microscopy. RESULTS. Transmission electron microscopy revealed SiNPs were taken up by keratocytes inside cytoplasmic vacuoles. Neither nuclear entry of SiNPs nor mitochondrial structural damage was observed. Both intracellular ROS generation and LDH level remained unchanged with up to 100 μg/mL SiNP treatment. Cellular viability was not affected by SiNP treatment. Autophagy showed significant dose-dependent activation with 50- and 100-nm SiNPs. However, mTOR activation remained unchanged. Vimentin expression did not show any significant increase with SiNPs. CONCLUSIONS. Our findings suggested that 50-, 100-, and 150-nm SiNPs did not induce significant cytotoxicity in cultured human keratocytes at concentrations up to 100 μg/mL.

Original languageEnglish (US)
Pages (from-to)362-371
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Silicon Dioxide
Nanoparticles
Autophagy
Vimentin
Sirolimus
Transmission Electron Microscopy
L-Lactate Dehydrogenase
Reactive Oxygen Species
Drug Carriers
Vacuoles

Keywords

  • Autophagy
  • Keratocyte
  • MTOR
  • Nanoparticle
  • Nanotoxicity
  • Silica
  • Viability

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

The effects of nonporous silica nanoparticles on cultured human keratocytes. / Yim, Bora; Park, Joo Hee; Jeong, Hyejoong; Hong, Jinkee; Shin, Young Joo; Chuck, Roy S.; Park, Choul Yong.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 1, 01.01.2017, p. 362-371.

Research output: Contribution to journalArticle

Yim, Bora ; Park, Joo Hee ; Jeong, Hyejoong ; Hong, Jinkee ; Shin, Young Joo ; Chuck, Roy S. ; Park, Choul Yong. / The effects of nonporous silica nanoparticles on cultured human keratocytes. In: Investigative Ophthalmology and Visual Science. 2017 ; Vol. 58, No. 1. pp. 362-371.
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AB - PURPOSE. Silica nanoparticles (SiNPs) are promising carriers for ophthalmic drug delivery. In this study, we investigated the effect of various sizes of nonporous SiNPs on cultured human keratocytes. METHODS. Three different sizes of SiNPs (50, 100, and 150 nm) were manufactured. Primarily cultured human keratocytes were exposed to different concentrations (0, 25, 50, and 100 μg/ mL) of three sizes of SiNPs for up to 72 hours. Intracellular reactive oxygen species (ROS) generation, cellular viability, lactate dehydrogenase (LDH) assay, autophagy, vimentin expression, and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of SiNPs was evaluated with transmission electron microscopy. RESULTS. Transmission electron microscopy revealed SiNPs were taken up by keratocytes inside cytoplasmic vacuoles. Neither nuclear entry of SiNPs nor mitochondrial structural damage was observed. Both intracellular ROS generation and LDH level remained unchanged with up to 100 μg/mL SiNP treatment. Cellular viability was not affected by SiNP treatment. Autophagy showed significant dose-dependent activation with 50- and 100-nm SiNPs. However, mTOR activation remained unchanged. Vimentin expression did not show any significant increase with SiNPs. CONCLUSIONS. Our findings suggested that 50-, 100-, and 150-nm SiNPs did not induce significant cytotoxicity in cultured human keratocytes at concentrations up to 100 μg/mL.

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