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Disaster - College of Veterinary Medicine - Texas A&M University

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Research<br />

Spotlight<br />

From drug delivery systems to cosmetics, the science <strong>of</strong><br />

nanotechnology has a wide range <strong>of</strong> applications. This science<br />

is based on the unusual properties that materials exhibit when<br />

their dimensions are reduced to the nanoscale, that is, to less<br />

than 100 nanometers (which is 1000 times smaller than the width<br />

<strong>of</strong> a human hair). For example, while inert at normal scales,<br />

gold nanoparticles are catalytically active and are being used to<br />

improve the performance <strong>of</strong> fuel cells. Further, unlike its bulk<br />

form, zinc oxide nanoparticles have better UV blocking properties,<br />

making them ideal for use in sunscreens.<br />

While the unique properties <strong>of</strong> nanoparticles are being<br />

exploited to generate a range <strong>of</strong> products, questions about the<br />

potential toxicity <strong>of</strong> these particles have not been adequately<br />

addressed. For example, how do nanoparticles incorporated<br />

into food matrices to increase longevity and freshness affect the<br />

immune system? How does inhaling an aerosolized mixture <strong>of</strong><br />

nanoparticles affect the lungs?<br />

Such questions are the focus <strong>of</strong> Dr. Christie Sayes’ research<br />

at the <strong>Texas</strong> A&M <strong>University</strong> <strong>College</strong> <strong>of</strong> <strong>Veterinary</strong> <strong>Medicine</strong> &<br />

Biomedical Sciences. Sayes, an assistant pr<strong>of</strong>essor in the department<br />

<strong>of</strong> <strong>Veterinary</strong> Physiology & Pharmacology, and her research<br />

group are at the forefront <strong>of</strong> a relatively new and rapidly developing<br />

field—nanotoxicology.<br />

Toxicity studies<br />

The toxic effects <strong>of</strong> nanoparticles are attributed to their<br />

various physicochemical properties, for example, size, surface<br />

reactivity, optical and electronic properties, agglomeration state<br />

and composition.<br />

“Studies in my laboratory and in the labs I was trained in, as<br />

well as the experiences <strong>of</strong> our collaborators all over the world<br />

[have indicated] that nanoparticle exposure results in inflammatory<br />

responses [for example, through the generation <strong>of</strong> reactive<br />

oxygen species],” Sayes said.<br />

“We’ve seen membrane oxidation,<br />

protein oxidation and even<br />

DNA oxidation.”<br />

In a previous study, Sayes<br />

showed that at high concentrations,<br />

nanoscale titanium<br />

dioxide particles, which are<br />

used in solar cells, for example,<br />

disrupted the normal activity <strong>of</strong><br />

human dermal fibroblasts and<br />

human lung epithelial cells in<br />

culture through oxidative dam-<br />

Top image: A human skin cell<br />

exposed to green quantum dots,<br />

which preferentially associate with<br />

the cell’s mitochondria.<br />

Bottom Image: A human skin cell<br />

exposed to green quantum dots<br />

encapsulated in polymer<br />

microcapsules. The red stain shows<br />

the healthy morphology <strong>of</strong> the cell<br />

by highlighting the cytoplasm.<br />

14 • CVM Today • Summer 2010<br />

Nanotoxicology:<br />

Exposing hidden dangers<br />

by Roma Subramanian<br />

age. Further, she has<br />

shown that depending<br />

on their surface<br />

reactivity, nanoquartz<br />

particles intratracheally<br />

instilled<br />

in rats produced<br />

different degrees <strong>of</strong><br />

pulmonary inflammation<br />

and cytotoxicity.<br />

These and other<br />

studies conducted<br />

by her lab on the<br />

biological effects <strong>of</strong><br />

different types <strong>of</strong><br />

nanoparticles have<br />

(From left to right) Michael Berg,<br />

helped provide evi-<br />

Aishwarya Sooresh, Dr. Christie Sayes,<br />

dence for nanopar- Nivedita Banerjee, and Amelia Romoser<br />

make up the research team studying<br />

ticle toxicity.<br />

nanoparticles.<br />

Currently, Sayes’<br />

lab is investigating the mechanisms underlying nanoparticleinduced<br />

inflammatory cascades and adverse immune responses.<br />

“Some <strong>of</strong> the cells in the body look at nanoparticles as antigens,<br />

and it’s the [resulting] increase in antibody production<br />

that’s really interesting,” Sayes said. “We know that antibodies<br />

are recruited, but do antibodies know to bind to nanoparticles to<br />

get rid <strong>of</strong> them? Can macrophages [cells involved in the body’s<br />

defense response] see nanoparticles and if not, will the particles<br />

persist in our body, or will we able to excrete them out?”<br />

The lab is also investigating the effect <strong>of</strong> a nanoparticle’s agglomeration<br />

state on cytotoxicity. Although nanocrystals, which<br />

can be in the form <strong>of</strong> a powder, tend to agglomerate in water,<br />

this agglomeration is not irreversible.<br />

“As nanoparticles move from one compartment <strong>of</strong> the body to<br />

another, they could de- and then reagglomerate,” Sayes said. “For<br />

example, when an agglomeration <strong>of</strong> nanoparticles gets immersed<br />

in lung surfactant fluid [secreted by lung alveolar cells], you<br />

sometimes immediately see a deagglomeration <strong>of</strong> particles, that<br />

is, the particles separate from each other.”<br />

Since cells appear to treat individual nanoparticles differently<br />

from the way they treat nanoparticle agglomerates, Sayes is interested<br />

in investigating the differential cellular uptake mechanisms<br />

<strong>of</strong> individual versus aggregated nanoparticles.<br />

Also, in collaboration with Swansea <strong>University</strong>, UK, Sayes’<br />

lab is investigating the toxicological effects <strong>of</strong> nanoparticles in<br />

composited materials. The project will examine whether in a car<br />

crash involving car bumpers made <strong>of</strong> nanomaterial composites,<br />

the nanoparticles embedded in the composited material are<br />

released and if so, whether they retain their physical and chemical<br />

characteristics and what would be the implications for the<br />

environment or human health.<br />

Challenges<br />

“The dose makes the poison,” is an <strong>of</strong>t repeated maxim in toxicology.<br />

However, the absence <strong>of</strong> a standardized unit to express

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