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Future Treatment of Oxidative-Stress Related Disorders with Nanotechnology. Dr. Beverly A Rzigalinski Virginia College of Osteopathic Medicine Virginia Polytechnic & State University Blacksburg, VA. Cerium Oxide. Cerium - Rare earth element Cerium atom surrounded by oxide lattice
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Dr. Beverly A Rzigalinski
Virginia College of Osteopathic Medicine
Virginia Polytechnic & State University
Blacksburg, VA
A Single Dose of Engineered Cerium Oxide
Nanoparticles Increases Brain Cell Longevity
Control
Nano-Treated
Days
Average Life Span
culture
27 DIV Organotypic brain cell
Culture treated with 10 nM Ceria
Nanoparticles at 10 DIV
123 DIV Organotypic brain cell
Culture treated with 10 nM Ceria
Nanoparticles at 10 DIV
Nanoparticle-Treated Cultures Maintain Normal Neuronal
Signaling Throughout Their Extended Lifespan
400
28 DIV Nano-Treated
28 DIV Control
300
[Ca2+]i
(nM)
200
68 DIV Nano-Treated
-
100
Time (Seconds)
100 mM Glutamate
O2
Free
Radical
O2
Ce+4
O2--x?
Cerium Oxide Nanoparticles Scavenge Hydroxyl Radicals
Generated by the Fenton Reaction
Fenton Reaction
+10 nm Ceria
+7 nm Ceria
+Fe-doped Ceria
Cerium Oxide Nanoparticles Scavenge
Superoxide Radicals
Irradiated
riboflavin
+7 nm Ceria
+10 nm Ceria
+Fe-doped Ceria
CeO2-Nanoparticles Have Activity SOD, GSH,
And Catalase-Like Activity
10 nm
7 nm
Activity
(Units)
SOD
Glutathione
Peroxidase
Catalase
Cerium Oxide Nanoparticles Protect Cells from
UV-Mediated Oxidative Stress
Cerium Oxide Nanoparticles Protect Cells Against Oxidative
Stress Induced by H2O2 - Size Dependency
Control
Control
160
160
Control
Control
50nm particles
50nm particles
50 nm Particles
50 nm Particles
20nm particles
20nm particles
10 nm Particles
10 nm Particles
140
140
7nm particles
7nm particles
7 nm Particles
7 nm Particles
120
120
4
100
100
80
80
Injured Cells x 10
60
60
40
40
4
20
20
Injured Cells x 10
0
0
m
m
m
m
Control 1nM 10nM 100nM 1
Control 1nM 10nM 100nM 1
M 10
M 10
M
M
Concentration
Concentration
Cerium Oxide Nanoparticles Protect Organotypic
Brain Cell Cultures From In Vitro Trauma
(10 nM, 10 DIV)
Injured
Cells/mg protein
(x 106)
n=16, in triplicate
7.5 mm
Injury
(Severe)
6.5 mm
Injury
(Moderate)
Uninjured
Cerium Oxide Nanoparticles Protect Organotypic
Brain Cell Cultures From In Vitro Trauma
4
_
Nano-Treated
1 hr Post Injury
_
Control
3
Injured
Cells/mg protein
(x 106)
_
2
_
1
7.5 mm
Injury
Uninjured
6.5 mm
Injury
No Response
No Response
D [Ca2+]i 100-265 nM
D [Ca2+]i 100-265 nM
D [Ca2+]i 100-265 nM
D [Ca2+]i >265 nM
D [Ca2+]i >265 nM
D [Ca2+]i >265 nM
Nanoparticles Preserve Normal Glutamate Signaling in Injured Neurons
120
Uninjured
100
24 Hr post
Moderate Injury
80
24 Hr post
Moderate Injury
Nano-Treated
Percentage
Of Neurons
Examined
60
40
20
0
+ 10 nm Ceria
Ceria Alone
Ceria + Albumin
Cerium Oxide Nanoparticles Block
Amyloid-beta –Induced Free Radical Production
Cerium Oxide Nanoparticles Protect Neurons from
Aβ(1-42) -Induced Toxicity
100
80
)
4
60
Total injured cells(x10
40
20
0
Control 10CeONP 100CeONP Aβ Aβ+10 CeONP Aβ+100CeONP
Treatment Groups
Cerium Oxide Nanoparticles Increase the Life Span
Of Female Drosophila and Maintain
Normal Geotaxis with Aging
100
80
60
Percent Survival
40
Control
20
10nM CeO2
0
0
20
40
60
80
Days
Geotactic Response
Control
m
100
1
M CeO2 NP
80
60
Percent Survival
40
20
0
1
3
5
7
24
48
72
Post-paraquat Time (in hours)
Cerium Oxide Nanoparticles Decrease Paraquat Toxicity
In Middle-Aged Female Drosophila
5 flies lived out
Normal lifespan
Eric Amateis
Matt Kurnick
Julie Karafakis
Clinical
Dr. Jill Cramer
Post Doctoral
Dr. Shaadi Elswaifi
Dr. Igor Danelison
Research Associates
Neeraj Singh
Courie Cohen
Kevin Hockey
Chine Logan
Collaborators
Dr. Kathleen Meehan
Dr. Rick Davis
Dr. David Cox
Nanophase Inc.
Advanced Powder Tech.
NanoNeuroLab at VCOM
