Simulated biological fluid exposure changes nanoceria's surface properties but not its biological response

Robert A. Yokel; Matthew L. Hancock; Benjamin Cherian; Alexandra J. Brooks; Marsha L. Ensor; Hemendra J. Vekaria; Patrick G. Sullivan; Eric A. Grulke

doi:10.1016/j.ejpb.2019.09.023

Simulated biological fluid exposure changes nanoceria's surface properties but not its biological response

Robert A. Yokel
, Matthew L. Hancock
, Benjamin Cherian
, Alexandra J. Brooks
, Marsha L. Ensor
, Hemendra J. Vekaria
, Patrick G. Sullivan
, Eric A. Grulke

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce³⁺ and Ce⁴⁺, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria's surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria's surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria's surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.

Original language	English
Pages (from-to)	252-265
Number of pages	14
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	144
DOIs	https://doi.org/10.1016/j.ejpb.2019.09.023
State	Published - Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Funding

This work was supported by the National Science Foundation REU Program #EEC-1460486 and the National Institutes of Health [grant number R01GM109195]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the following for their instruction and assistance: Andrew Colburn: zeta potential measurements, Soledad Yao: FT-IR; Nancy Miller: XRD; and Dr. Dali Qian: TEM. The authors declare that they have no competing interests. RAY conceived and coordinated the study, wrote drafts of the report, and coordinated report input from the authors. BC contributed to this work as a summer research student at the University of Kentucky. BC and AJB synthesized nanoceria and conducted initial studies of SBF-exposed nanoceria, that were followed up by MLH. MLH synthesized the nanoceria and conducted most of the nanoceria SBF exposures. EAG provided input on the nanoceria synthesis, purification, and SBF exposure; oversaw EM imaging; and conducted primary particle size determination and particle coating thickness estimations. MLE conducted the resazurin assays. HV conducted the Seahorse assays and result calculations. PS guided the interpretation of the Seahorse assay results. All authors approved the revised version of this report. This work was supported by the National Science Foundation REU Program #EEC-1460486 and the National Institutes of Health [grant number R01GM109195 ]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health . The authors thank the following for their instruction and assistance: Andrew Colburn: zeta potential measurements, Soledad Yao: FT-IR; Nancy Miller: XRD; and Dr. Dali Qian: TEM.

Funders	Funder number
AJB
National Science Foundation REU Program
National Science Foundation Arctic Social Science Program	-1460486
National Institutes of Health (NIH)
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	R01GM109195
University of Kentucky
The Ministry of Economic Affairs and Employment

Keywords

A549 cells
Body fluids
Caco-2 cells
Cellular respiration
Cerium
Engineered nanoparticles
Hydrodynamic diameter
Microscopy, electron, transmission
Nanoceria
Nanoparticle corona
Spectroscopy, Fourier transform infrared
Thermogravimetric analysis
X-ray diffraction

ASJC Scopus subject areas

Biotechnology
Pharmaceutical Science

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10.1016/j.ejpb.2019.09.023

Cite this

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title = "Simulated biological fluid exposure changes nanoceria's surface properties but not its biological response",

abstract = "Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria's surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria's surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria's surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.",

keywords = "A549 cells, Body fluids, Caco-2 cells, Cellular respiration, Cerium, Engineered nanoparticles, Hydrodynamic diameter, Microscopy, electron, transmission, Nanoceria, Nanoparticle corona, Spectroscopy, Fourier transform infrared, Thermogravimetric analysis, X-ray diffraction",

author = "Yokel, \{Robert A.\} and Hancock, \{Matthew L.\} and Benjamin Cherian and Brooks, \{Alexandra J.\} and Ensor, \{Marsha L.\} and Vekaria, \{Hemendra J.\} and Sullivan, \{Patrick G.\} and Grulke, \{Eric A.\}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2019",

month = nov,

doi = "10.1016/j.ejpb.2019.09.023",

language = "English",

volume = "144",

pages = "252--265",

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AU - Yokel, Robert A.

AU - Hancock, Matthew L.

AU - Cherian, Benjamin

AU - Brooks, Alexandra J.

AU - Ensor, Marsha L.

AU - Vekaria, Hemendra J.

AU - Sullivan, Patrick G.

AU - Grulke, Eric A.

PY - 2019/11

Y1 - 2019/11

N2 - Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria's surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria's surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria's surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.

AB - Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria's surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria's surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria's surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.

KW - A549 cells

KW - Body fluids

KW - Caco-2 cells

KW - Cellular respiration

KW - Cerium

KW - Engineered nanoparticles

KW - Hydrodynamic diameter

KW - Microscopy, electron, transmission

KW - Nanoceria

KW - Nanoparticle corona

KW - Spectroscopy, Fourier transform infrared

KW - Thermogravimetric analysis

KW - X-ray diffraction

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C2 - 31563633

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SN - 0939-6411

VL - 144

SP - 252

EP - 265

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

ER -

Simulated biological fluid exposure changes nanoceria's surface properties but not its biological response

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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