Академический Документы
Профессиональный Документы
Культура Документы
Journal of
Nanoscience and Nanotechnology
Vol. 10, 79197930, 2010
1
Department of Chemistry, San Diego State University, San Diego CA 92182 USA
Centro de Graduados e Investigacin del Instituto Tecnolgico de Tijuana, Apdo postal 1166, Tijuana, B. C. Mexico
REVIEW
In recent years, nanoparticles have received increasing attention in research and technology, including a variety of practical applications. The bioactivity appears to be related to the small particle
size, in addition to inherent chemical activity as electron transfer (ET) agents, generators of reactive oxygen species (ROS) with subsequent oxidative stress (OS) and as antioxidants (AOs). The
mechanism of toxicity, therapeutic action and AO property is addressed based on the ET-ROS-OS
approach. There are several main classes of ET functionalities, namely, quinones (or phenolic precursors), metal compounds, aromatic nitro compounds (or reduction products) and imine or iminium
species. Most of the nanospecies fall within the metal category. Cell signaling is also discussed.
This review is apparently the rst to address the various bioactivities based on the ET-ROS-OS-AO
framework.
Delivered
by Publishing
Technology
to: Antioxidants,
Universidad Therapeutics,
Nacional Autonoma
MexicoReactive
(UNAM)
Keywords:
Nanoparticles,
Toxicants,
Electronde
Transfer,
IP: 132.248.116.122
On: Mon, 09 Mar 2015 15:59:25
Oxygen
Species, Mechanisms.
Copyright: American Scientific Publishers
CONTENTS
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Nanoparticle Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1. Unintentionally Produced Nanoparticles . . . . . . . . . . . . . .
2.2. Combustion-Derived Nanoparticles (CDNP) . . . . . . . . . .
2.3. Diesel Exhaust Particulate (DEP) . . . . . . . . . . . . . . . . . . .
2.4. Aggregated Carbon and Carbonaceous Nanoparticles . . .
2.5. Organic Nanoparticulates . . . . . . . . . . . . . . . . . . . . . . . . .
2.6. Welding Fumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.7. Asbestos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.8. Engineered Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . .
2.9. Fullerenes (C60 ) and Carbon Nanotubes . . . . . . . . . . . . . .
3. Metal Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Titanium Dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2. Silicon Dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3. Iron and Iron Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4. Cerium Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5. Copper Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6. Zinc Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.7. Cobalt Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.8. Silver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.9. Quantum Dots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.10. Manganese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.11. Aluminum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.12. Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.13. Gold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7919
7921
7921
7921
7921
7921
7921
7922
7922
7922
7922
7923
7923
7924
7924
7925
7925
7925
7925
7925
7926
7926
7926
7926
7926
4. Nanoparticle Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5. Nanoparticle Theapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowlegment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References and Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7926
7927
7928
7928
1. INTRODUCTION
Nano has a longstanding use in science to mean one billionth (1 109 . The prex nano comes from the Greek
word meaning dwarf. Nanotechnology is the understanding
and control of matter on an atomic and molecular scale
at dimensions between 1 and 100 nanometers. Nanoparticles are chemically highly active, in part, because of
their large surface area proportional to their volume. This
causes formation of agglomerates in which particles are
held together by relatively weak forces, including van
der Waals forces, electrostatic forces and surface tension.
Nanoparticles may also form a group of strongly associated particles called aggregates. Nanoparticles less than
30 nm have markedly altered properties and are often
referred to as quantum dots because their size controls
the separation of energy levels within them, behaving like
a semiconductor. Nanoscale materials nd use in a variety of different areas, such as electronic, magnetic, optoelectronic, biomedical, pharmaceutical, cosmetic, energy,
1533-4880/2010/10/7919/012
doi:10.1166/jnn.2010.3028
7919
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
environmental, catalytic, and materials applications. Nanoalkyl peroxides, and diverse radicals (hydroxyl, alkoxyl,
technology is considered by many as the next step
hydroperoxyl, and superoxide [SO]). In some case, ET
in science, integrating engineering with biology, chemresults in interference with normal electrical effects (e.g.,
istry and physics. The potential of this technology has
in respiration or neurochemistry). Generally, active entitriggered a tremendous investment and investigation in
ties possessing ET groups display reduction potentials in
the academic and industrial worlds in recent years. The
the physiologically responsive range, (i.e., more positive
technology has moved from an exotic research pursuit to
than 0.5 V). ET, ROS, and OS have been increasingly
inclusion in hundreds of mainstream consumer products
implicated in the mode of action of drugs and toxins, e.g.,
with nanomaterial markets exceeding billions of dollars
antiinfective agents,9 anticancer drugs,10 carcinogens,11
annually. Many medical innovations, imaging, drug delivreproductive toxins,12 nephrotoxins,13 hepatotoxins,14 carery, nanotherapeutics and nanophase formulations, are in
diovascular toxins,15 nerve toxins,16 mitochondrial toxins,17
clinical trials. With this nanophase invasion of new materiabused drugs,18 ototoxins,19 immunotoxins,20 eye toxins,21
als and products into every aspect of life comes increasing
pulmonary toxins22 and various other categories.23
18
safety and exposure risk; several reviews have addressed
There is a plethora of experimental evidence supporting
this issue from an environmental and medical point of
the ET-ROS theoretical framework, including generation
view. It is recognized that nanoparticles produce reactive
of the common ROS, lipid peroxidation, degradation prodoxygen species (ROS) inside and outside the cell and is
ucts of oxidation, depletion of AOs, effect on exogethe key factor in toxicological effects.4 7
nous AOs, and DNA oxidation and cleavage products, as
Electron transfer (ET) is probably the most imporwell as electrochemical data. This comprehensive, unitant process in chemical transformations. Large impefying mechanism is in keeping with the frequent obsertus was provided to the area by Marcus theory. The
vations that many ET substances display a variety of
preponderance of bioactive substances or their metaboactivities (e.g., multiple-drug properties) as well as toxic
lites incorporate ET functionalities, which, we believe,
effects.
play an important role in physiological responses. The
This review provides a unifying mechanism for the
main groups include quinones (or phenolic precursors),
physiological action of nanoparticles, involving toxicity,
metal complexes (or complexors), aromatic nitro comantioxidant effects and therapeutic use. Apparently, this
Publishing Technology
Universidad
Nacional
Autonoma
deET-ROS-OS
Mexico (UNAM)
pounds (orDelivered
reduced by
hydroxylamine
and nitroso to:
derivaarticle
is the rst
based on
in the mode of
132.248.116.122
On: Mon,
09 Mar
2015 15:59:25
tives), and conjugated imines (orIP:iminium
species). In vivo
action.
However,
it is important to recognize that biologAmerican
Publishers
redox cycling with oxygen can occur, Copyright:
giving rise to
oxida- Scientific
ical action
is often complex entailing a variety of factors.
tive stress (OS) through generation of reactive oxygen
Literature references are mainly representative with origispecies (ROS), such as hydrogen peroxide, hydroperoxides,
nal ones present in prior reviews in some cases.
Peter Kovacic was born in Pennsylvania in 1921, graduated (BA) from Hanover College,
obtained Ph.D. from the University of Illinois, did postdoctoral work at MIT, was instructor
at Columbia University and research chemist at Du Pont. His academic carrier was spent at
Case Western Reserve University and the University of Wisconsin-Milwaukee. After being
a Visiting Professor at about a dozen universities, he is currently Adjunct Professor at San
Diego State University, working on fundamental mechanisms of physiological agents.
Ratnasamy Somanathan was born in Sri Lanka (Ceylon) in 1942, graduated (B.Sc.)
from University of Ceylon (Sri Lanka Peradeniya), obtained Ph.D. from the University of
Shefeld, England, did postdoctoral work at University of Liverpool, England and University of California Davis. Currently Professor at the Center for Graduate Studies, Institute of
Technology Tijuana, Mexico and Adjunct Professor at San Diego State University.
7920
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
2. NANOPARTICLE TOXICITY
2.1. Unintentionally Produced Nanoparticles
give rise to CDNP,28 with diesel producing more particles per unit fuel than gasoline. Animal studies demonstrate that DEP and other nanoparticulate forms of carbon
are carcinogenic.29 Studies have also shown the adjuvant effects of diesel particles on the intensity of allergic
responses. These effects could also be mediated indirectly
through inammation and oxidative stress.30 31 It was
shown that diesel exhaust, as well as titanium dioxide particles can directly induce cardiac cell damage and affect
the function of the cells through ROS formation.32 In an
epidemiological study, inhalation of diesel exhaust induced
epithelial cells in the lung, generating cell-damaging intracellular ROS.33 Recent reviews implicate reactive oxygen
species in the mechanism of action related to particleinduced oxidative stress and oxidation of DNA3 34 and
CNS diseases.35
7921
REVIEW
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
7923
REVIEW
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
CeO2 nanoparticles when tested with human lung epithelial cells led to cell death, with increase in ROS, decrease
in GSH and the induction of oxidative stress-related
genes, such as heme oxygenase-1, catalase, glutathione
s-transferase, and thioredoxin reductase.87 In a related
study, CeO2 nanoparticles were shown to exert toxicity
through oxidative stress, as they cause signicant increase
in the cellular ROS concentrations, subsequently leading
to the strong induction of heme oxygenase-1 via the p383.7. Cobalt Oxide
88
Nrf-2 signaling
pathway.
Delivered
by Publishing Technology to: Universidad Nacional Autonoma de Mexico (UNAM)
Cobalt
oxide,
when
tested on a human cell line, enters the
IP: 132.248.116.122 On: Mon,
09 Mar
2015
15:59:25
cells
very
rapidly
and
causes a rapid induction of ROS if
Copyright:
American
Scientific
Publishers
3.5. Copper Oxide
supplied in the form of Co3 O4 nanoparticles, rather than
Metal oxide nanoparticles are often used as industrial cations.95
alysts, and elevated levels of these particles have been
clearly demonstrated at sites surrounding factories. To
3.8. Silver
date, limited toxicity data on these nanoparticles are availSilver namometal has been used in many consumer
able. Comparison was made of different metal oxide
applications, mostly because of its well-demonstrated
nanoparticles (Cu, Ti, Zn and Fe) in relation to toxicity,
89
and presumed safe use as an antimicrobial agent. Silver
DNA damage and oxidative lesions. Cu nanoparticles
nanoparticles in the sub-50 nm range exhibit increased
were the most potent regarding cytotoxicity, oxidative
efcacy in inhibiting a wide range of bacteria and fungi.
lesions and DNA damage. In a related study, epithelial
Although silver nanoparticles are already found widely
(HEp-2) cells were exposed to SiO2 , Fe2 O3 , and CuO
in multiple products, a concrete assessment of its effects
nanoparticles. CuO induced the greatest amount of cytoon human health and environmental implications remains
toxicity in a dose dependent manner. Although all metal
lacking.
oxide nanoparticles were able to generate ROS in HEp-2
Carlson et al. have shown size dependent toxicity
cells, CuO was better able to overwhelm antioxidant
of silver nanoparticles, largely mediated through oxidadefenses, e.g., catalase and glutathione.90 They were the
tive stress.96 The effect of Ag-25 nanoparticles on mice
only particle that caused a signicant increase in intrabrain was studied. RNA was isolated from the frontal
cellular ROS. It is important to distinguish effects of
cortex and hippocampus regions. Data suggest Ag-25
nanoparticles from dissolved metals.91 Nanocopper pronanoparticles may produce neurotoxicity by generating
duced different morphological effects and gene expression
free radical-induced OS and by altering gene exprespatterns than did soluble copper. Also, Cu nanoparticles
sion, producing apoptosis and neurotoxicity.97 A study
were toxic to plants.92 Since cupric ion released from
revealed the OS-dependent toxicity of silver nanopartiCu nanoparticles had neglible effects, the toxicity clearly
cles in human hepatoma cells. However, the toxicity and
resulted from the Cu nanoparticles. There is evidence that
DNA damage were prevented by use of the antioxidant
free radicals may contribute to toxicity by Cu.13 Wilsons
N -acetylcysteine.98 A systematic study on the in vitro
disease, a condition characterized by toxic levels of the
metal, seems to involve copper-stimulated free-radical
interactions of spherical silver nanoparticles with HT-1080
J. Nanosci. Nanotechnol. 10, 79197930, 2010
7925
REVIEW
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
4. NANOPARTICLE ANTIOXIDANTS
The prior portion of this review provides extensive evidence for participation of nanoparticles in the generation
of ROS and OS. There is an apparent dichotomy since the
following section documents many reports of these entities
in the role of AOs. A rationale can be provided. In the case
of OS, the particles may be acting as ET agents by transferring electrons to oxygen with formation of superoxide,
a precursor of other ROS. With regard to AO action, it is
known that nanoparticles, e.g., the C60 type,113 can absorb
J. Nanosci. Nanotechnol. 10, 79197930, 2010
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
7927
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
REVIEW
7928
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
7929
REVIEW
55. L. Harhaji, A. Isakovic, N. Raicevic, Z. Markovic, B. Todorovic85. M.-T. Zhu, W.-Y. Feng, B. Wang, T.-C. Wang, Y.-Q. Gu, M. Wang,
Markovic, N. Nikolic, S. Vranjes-Djuric, I. Markovic, and
Y. Wang, H. Ouyang, Y.-L. Zhao, and Z.-F. Chai, Toxicology
V. Trajkovic, Eur J. Pharmacol. 568, 89 (2007).
247, 102 (2008).
56. X. Zhu, L. Zhu, and Y. Chen, Environ. Toxicol. Chem. 27, 1979
86. W. J. Waldman, R. Kristovich, D. A. Knight, and P. K. Dutta, Chem.
(2008).
Res. Toxicol. 20, 1149 (2007).
57. T. M. Bickley and P. McClellan-Green, Environ. Toxicol. Chem.
87. E. J. Park, J. Choi, Y.-K. Park, and K. Park, Toxicology 245, 90
27, 1964 (2008).
(2008).
58. C. M. Sayes, A. A. Marchione, K. L. Reed, and D. B. Warheit,
88. H.-J. Eom and J. Choi, Toxicol. Lett. 187, 77 (2009).
Nano Lett. 7, 2399 (2007).
89. H. L. Karlsson, P. Cronholm, J. Gustafsson, and L. Mller, Chem.
59. L. Brunet, D. Y. Lyon, E. M. Hotze, P. J. Alvarez, and M. R.
Res. Toxicol. 21, 1726 (2008).
Wiesner, Environ. Sci. Technol. 43, 4355 (2009).
90. B. Fahmy and S. A. Cormier, Toxicol. Vitro 23, 1365 (2009).
60. M. S. Misirkic, M. Todorovic-Markovic, L. M. Vucicevic, K. D.
91. R. J. Griftt, R. Weil, K. A. Hyndman, N. D. Denslow, K. Powers,
Janjetovic, V. R. Jokanovic, M. D. Dramicanin, Z. M. Markovic,
D. Taylor, and D. S. Barber, Environ. Sci. Technol. 41, 8178 (2007).
and V. S. Trajkovic, Biomaterials 30, 2319 (2009).
92. W. M. Lee, Y. J. An, H. Yoon, and H. S. Kweon, Environ. Toxicol.
61. M. J. Jou, Adv. Drug Deliv. Rev. 60, 13 (2008).
Chem. 27, 1915 (2008).
62. P. Kovacic and R. Somanathan, In Antioxidants: New Research,
93. G. M. Bishop, R. Dringen, and S. R. Robinson, Free Rad. Biol.
edited by H. V. Panglossi, Nova Science Publishers Inc., NY
Med. 42, 1222 (2007).
(2006), p. 1.
94. T. Xia, M. Kovochich, M. Liong, L. Mdler, B. Gilbert, H. Shi,
63. C. Blaise, F. Gagn, J. F. Frard, and P. Eullaffroy, Environ. Toxicol.
J. I. Yeh, J. I. Zink, and A. E. Nel, ACS Nano 2, 2121 (2008).
23, 591 (2008).
95. E. Papis, F. Rossi, M. Raspanti, I. Dalle-Donne, G. Colombo,
64. N. R. Jacobsen, G. Pojana, P. White, P. Mller, C. A. Cohn,
A Milzani, G. Bernardini, and R. Gornati, Toxicol. Lett. 189, 253
K. S. Korsholm, U. Vogel, A. Marcomini, S. Loft, and H. Wallin,
(2009).
Environ. Mol. Mutagen 49, 476 (2008).
96. C. Carlson, S. M. Hussain, A. M. Schrand, L. K. Braydich-Stolle,
65. J. P. Ryman-Rasmussen, M. F. Ceta, A. R. Brody, J. K. ShipleyK. L. Hess, R. L. Jone, and J. J. Schlager, J. Phys. Chem. B
Phillips, J. I. Everitt, E. W. Tewksbury, O. R. Moss, B. A. Wong,
112, 13608 (2008).
D. E. Dodd, M. E. Andersen, and J. C. Bonner, Nat. Nanotechnol.
97. M. F. Rahman, J. Wang, T. A. Patterson, U. T. Saini, B. L.
4, 747 (2009).
Robinson, G. D. Newport, R. C. Murdock, J. J. Schlager, S. M.
66. A. R. Murray, E. Kisi, S. S. Leonard, S. H. Young, C. Kommineni,
Hussain, and S. F. Ali, Toxicol. Lett. 187, 15 (2009).
V. E. Kagan, V. Castranova, and A. A. Shvedova, Toxicology
98. S. Kim, J. E. Choi, J. Choi, K.-H. Chung, K. Park, J. Yi, and D.-Y.
257, 161 (2009).
Rye, Toxicol. Vitro 23, 1076 (2009).
67. H. Yang, C. Liu, D. Yang, H. Zhang, and Z. Xi, J. Appl. Toxicol.
99. S. Arora, J. Jain, J. M. Rajwade, and K. M. Paknikar, Toxicol. Lett.
29, 69 Delivered
(2009).
by Publishing Technology to: Universidad Nacional
Autonoma de Mexico (UNAM)
179, 93 (2008).
68. P. Kovacic, Birth Defects Res. Part
78, 333 (2006).
IP:C 132.248.116.122
On: Mon,
09
Mar
2015
15:59:25
100. S. M. Hussain, K. L. Hess, J. M. Gearhart, K. T. Geiss, and J. J.
69. T. C. Long, J. Tajuba, P. Sama, N. Saleh,
C. Swartz,American
J. Parker, Scientific Publishers
Copyright:
Schlager, Toxicol. Vitro 19, 975 (2005).
S. Hester, G. V. Lowrt, and B. Veronesi, Environ. Health Perspect.
101. T. Yoshimaru, Y. Suzuki, T. Inoue, O. Niide, and C. Ra, Free Rad.
115, 1631 (2007).
Biol. Med. 40, 1949 (2006).
70. S. J. Kang, B. M. Kim, Y. J. Lee, and H. W. Chung, Environ. Mol.
102. C. N. Lok, C. M. Ho, R. Chen, Q. Y. He, W. Y. Yu, H. Sun, P. K.
Mutagen 49, 399 (2008).
Tam, J. F. Chiu, and C. M. Che, J. Biol. Inorg. Chem. 12, 527
71. J. Wang, Y. Liu, F. Jiao, F. Lao, W. Li, Y. Gu, Y. Li, C. Ge, G. Zhou,
(2007).
B. Li, Y. Zhao, Z. Chai, and C. Chen, Toxicology 254, 82 (2008).
103. J. F. Hernndez-Sierra, F. Ruiz, D. C. Pena, F. Martinez72. J. F. Reeves, S. J. Davies, N. J. F. Dodd, and A. N. Jha, Mutat.
Gutirrez, A. E. Martinez, J. Guilln Ade, and G. M. Tapia-Pnn,
Res. 640, 113 (2008).
Nanomedicine 4, 237 (2008).
73. J.-X. Wang, Y.-B. Fan, Y. Gao, Q.-H. Hu, and T.-C. Wang,
104. H.-L. Su, C.-C. Chou, D.-J. Hung, S.-H. Lin, J.-C. Pao, J.-H. Lin,
Biomaterials 30, 4590 (2009).
F.-L. Huang, R.-X. Dong, and J.-J. Lin, Biomaterials 30, 5979
74. E.-J. Park, J. Yi, K.-H. Chung, D.-Y. Ryu, J. Choi, and K. Park,
(2009).
Toxicol. Lett. 180, 222 (2008).
105. J. Kim, H.-J. Park, J.-H. Lee, J.-S. Hahn, M. B. Gu, and J. Yoon,
75. V. Brezov, S. Gabcov, D. Dvoranov, and A. Stako,
Water Res. 43, 5252 (2009).
J. Photochem. Photobiol. B: Biol. 79, 121 (2005).
106. J. Lovric, S. J. Cho, F. M. Winnik, and D. Maysinger, Chem. Biol.
76. B. Rothen-Rutishauser, L. Mueller, F. Blank, C. Brandenberger,
12, 1227 (2005).
C. Muehfeld, and P. Gehr, ALTEX 25, 191 (2008).
107. S. J. Cho, D. Maysinger, M. J. Jain, B. Rder, S. Hackbarth, and
77. T. J. Brunner, P. Wick, P. Manser, P. Spohn, R. N. Grass, L. K.
F. M. Winnik, Langmuir 23, 1974 (2007).
Limbach, A. Bruinink, and W. J. Stark, Environ. Sci. Tech. 40, 4374
108. K. G. Li, J. T. Chen, S. S. Bai, X. Wen, S. Y. Song, Q. Yu, J. Li,
(2006).
and Y. Q. Wang, Toxicol. Vitro 23, 1007 (2009).
78. L. K. Adams, D. Y. Lyon, and A. J. J. Alvarez, Water Res. 40, 3527
109. J. Liang, Z. He, S. Zhang, S. Huang, X. Ai, H. Yang, and H. Han,
(2006).
Talanta 71, 1675 (2007).
79. F. Wang, F. Gao, M. Lan, H. Yuan, Y. Huang, and J. Liu, Toxicol.
110. S. M. Hussain, A. K. Javorina, A. M. Schrand, H. M. Duhart, S. F.
Vitro 23, 808 (2009).
Ali, and J. J. Schlager, Toxicol. Sci. 92, 456 (2006).
80. W. Lin, Y.-W. Huang, X.-D. Zhou, and Y. Ma, Toxicol. Appl.
111. M. D. Cheng, J. Environ. Sci. Health A Tox. Hazard Subst. Environ.
Pharmacol. 217, 252 (2006).
Eng. 39, 2691 (2004).
81. E.-J. Park and K. Park, Toxicol. Lett. 184, 18 (2009).
112. H. Liu, Y. Tian, and P. Xia, Langmuir 24, 6359 (2008).
82. H.-J. Eom and J. Choi, Toxicol. Vitro 23, 1326 (2009).
113. C. Wang, L. A. Tai, D. D. Lee, P. P. Kanakamma, C. K.-F. Shen,
83. A. Alekseenko, Y. V. Waseem, and S. V. Fedorovich, Brain Res.
T.-Y. Luh, C. H. Cheng, and K. C. Hwang, J. Med. Chem. 42, 4614
1241, 193 (2008).
(1999).
84. P. L. Apopa, Y. Qian, R. Shao, N. L. Guo, D. Schwegler-Berry,
114. P. Spohn, C. Hirsch, F. Hasler, A. Bruinink, H. F. Krug, and
M. Pacurari, D. Porter, X. Shi, V. Vallyathan, V. Castranova, and
P. Wick, Environ. Pollution 157, 1134 (2009).
D. C. Flynn, Part Fibre Toxicol. 6, 1 (2009).
REVIEW
Biomechanisms of Nanoparticles (Toxicants, Antioxidants and Therapeutics): Electron Transfer and ROS
115. J.-J. Yin, F. Lao, P. P. Fu, W. G. Wamer, Y. Zhao, P. C. Wang,
Y. Qjiu, B. Sun, G. Xing, J. Dong, X.-J. Liang, and C. Chen,
Biomaterials 30, 611 (2009).
116. G. V. Andrievsky, V. I. Bruskov, A. A. Tykhomyrov, and S. V.
Gudov, Free Rad. Biol. Med. 47, 786 (2009).
117. M. S. Misirkic, B. M. Todoroviv-Markovic, L. M. Vucicevic, K. D. Janjetovic, V. R. Jokanovic, M. D. Dramicanin,
Z. M. Markovic, and V. S. Trajkovic, Biomaterials 30, 2319
(2009).
118. J. J. Ryan, H. R. Bateman, A. Stover, G. Gomez, S. K. Norton,
W. Zhao, L. B. Schwartz, R. Lenk, and C. L. Kepley, J. Immunol.
179, 665 (2007).
119. S. Onizawa, K. Aoshiba, M. Kajita, Y. Miyamoto, and A. Nagai,
Pulmonary Pharmacol. Therapeut. 22, 340 (2009).
120. M. Kajita, K. Hikosaka, M. Iitsuka, A. Kanayama, N. Toshima, and
Y. Miyamoto, Free Radic. Res. 41, 615 (2007).
121. L. Kim, M. Takahashi, T. Shimizu, T. Shirasawa, M. Kajita,
A. Kanayama, and Y. Miyamoto, Mech. Ageing Develop. 129, 322
(2008).
122. J. Chen, S. Patil, S. Seal, and J. F. McGinnis, Nat. Nanotechnol.
1, 142 (2006).
123. J. Wang, C. Chen, B. Li, H. Yu, Y. Zhao, J. Sun, Y. Li, G. Xing,
H. Yuan, J. Tang, Z. Chen, H. Meng, Y. Gao, C. Ye, Z. Chai,
C. Zhu, B. Ma, X. Fang, and L. Wan, Biochem. Pharmacol. 71, 872
(2006).
124. T.-H. Wu, F.-L. Yen, L.-T. Lin, T.-R. Tsai, C.-C. Lin, and T.-M.
Cham, Int. J. Pharmaceutics 346, 160 (2008).
125. J. Niu, A. Azfer, L. M. Rogers, X. Wang, and P. E. Kolattukudy,
Cardiovascular Res. 73, 549 (2007).
126. D. Schubert, R. Darusch, J. Raitano, and S.-W. Chan, Biochem.
Biophys. Res. Commun. 342, 86 (2006).
127. H. Wang, W. Wei, S.-Y. Sheng, Y.-X. Shen, Y. Li, N.-P. Wang, and
S.-Y. Xu, J. Pineal Res. 39, 156 (2005).
128. T. B. Shea, D. Ortiz, R. J. Nicolosi, R. Kumar, and A. C. Watterson,
J. Alzheimers Dis. 7, 297 (2005).
129. R. Bawa, Nanotechnol. Law Business 5, 135 (2008).
130. J. Jain, S. Arora, J. Rajwade, S. Khandelwal, and K. M. Pakniker,
Mol. Pharm. 6, 1388 (2009).
131. J. F. Kukowska-Latalo, K. A. Candido, Z. Cao, S. S. Nigavekar,
I. J. Majoros, T. P. Thomas, L. P. Balogh, and M. K. Khan, Cancer
Res. 65, 5317 (2005).
132. M. E. Davis, Z. Chen, and D. M. Shin, Nature Rev. Drug Discov.
7, 771 (2008).
133. A. Lamprechet, H. Yamamoto, H. Takeuchi, and Y. Kawashima,
J. Pharmacol. Exper. Therapeut. 315, 196 (2005).
134. A. Z. Wang, F. Gu, L. Zhang, J. M. Chan, A. Radovic-Moreno,
M. R. Shaikh, and O. C. Farokhzad, Expert Opin. Biol. Ther.
8, 1063 (2008).
135. Y.-Y. Yang, Y. Wang, R. Powell, and P. Chen, Clin. Exp.
Pharmacol. Physiol. 33, 557 (2006).
7930