The Technion Researchers Find to NanoParticles may Threaten Heart

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system. Their study is published in the December 2014 issue of Environmental Toxicology.

Prof. Michael Aviram
The research team was comprised of scientists from the Technion Rappaport Faculty of Medicine, Rambam Medical Center, and the Center of Excellence in Exposure Science and Environmental Health (TCEEH).

“Environmental exposure to nanoparticles is becoming unavoidable due to the rapid expansion of nanotechnology,” says the study’s lead author, Prof. Michael Aviram, of the Technion Faculty of Medicine, “This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Products that use silica-based nanoparticles for biomedical uses, such as various chips, drug or gene delivery and tracking, imaging, ultrasound therapy, and diagnostics, may also pose an increased cardiovascular risk for consumers as well.”

In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress – are converted into lipids, or laden “foam cells” which, in turn, accelerate atherosclerosis development.

“Macrophage foam cells accumulation in the arterial wall are a key cell type in the development of atherosclerosis, which is an inflammatory disease” says co-author Dr. Lauren Petrick. “The aims of our study were to gain additional insight into the cardiovascular risk associated with silicon dioxide nanoparticle exposure and discover the mechanisms behind Si02’s induced atherogenic effects on macrophages. We also wanted to use nanoparticles as a model for ultrafine particle (UFP) exposure as cardiovascular disease risk factors.”

Both NPs and UFPs can be inhaled and induce negative biological effects. However, until this study, their effect on the development of atherosclerosis has been largely unknown. Here, researchers have discovered for the first time that the toxicity of silicon dioxide nanoparticles has a “significant and substantial effect on the accumulation of triglycerides in the macrophages,” at all exposure concentrations analyzed, and that they also “increase oxidative stress and toxicity.”

A recent update from the American Heart Association also suggested that “fine particles” in air pollution leads to elevated risk for cardiovascular diseases. However, more research was needed to examine the role of “ultrafine particles” (which are much smaller than “fine particles”) on atherosclerosis development and cardiovascular risk.

“The number of nano-based consumer products has risen a thousand fold in recent years, with an estimated world market of $3 trillion by the year 2020,” conclude the researchers. “This reality leads to increased human exposure and interaction of silica-based nanoparticles with biological systems. Because our research demonstrates a clear cardiovascular health risk associated with this trend, steps need to be taken to help ensure that potential health and environmental hazards are being addressed at the same time as the nanotechnology is being developed.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

American Technion Society (ATS) donors provide critical support for the Technion—more than $1.95 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.

Source: ATS

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Engineers develop new sensor to detect tiny individual nanoparticles

The image shows arrays of self-referenced and self-heterodyned Whispering-Gallery Raman microlasers for single nanoparticle detection. A "pump" laser generates a single Raman lasing mode inside the silica resonators. Upon landing of a nanoparticle on the resonator, Raman laser circulating inside the resonator undergo mode splitting leading to two new lasing modes in different colors. Monitoring the changes in the color difference (frequency difference) enables detecting and measuring of nanoparticles with single particle resolution. Credit: J. Zhu, B. Peng, S.K. Ozdemir, L. Yang

Nanoparticles, engineered materials about a billionth of a meter in size, are around us every day. Although they are tiny, they can benefit human health, as in some innovative early cancer treatments, but they can also interfere with it through viruses, air pollution, traffic emissions, cosmetics, sunscreen and electronics.

A team of researchers at Washington University in St. Louis, led by Lan Yang, PhD, the Das Family Career Development Associate Professor in Electrical & Systems Engineering, and their collaborators at Tsinghua University in China have developed a new sensor that can detect and count nanoparticles, at sizes as small as 10 nanometers, one at a time. The researchers say the sensor could potentially detect much smaller particles, viruses and small molecules.

The research appears in the Proceedings of the National Academy of Sciences online Early Edition Sept. 1, 2014.

Yang and her colleagues have created the Raman microlaser sensor in a silicon dioxide chip to find individual nanoparticles without the need to "dope" the chip with chemicals called rare-earth ions to provide optical gain for the microlaser. Incorporating additions to the microresonator creates the need for more processing steps and increased costs and invites biocompatibility risks. In addition, the use of rare-earth ions requires specific "pump" lasers matching the energy transitions of the ions to generate optical gain, so for different rare-earth ions, different pump lasers must be used. Using the Raman process loosens the requirement of specific wavelength bands for pump lasers because Raman gain can be obtained using pump at any wavelength band, Yang says.

"This gives us the advantage of using the same dopant-free sensor at different sensing environments by tailoring the lasing frequency for the specific environment, for example, at the band where the environment has minimum absorption, and for the properties of the targeted nanoparticles by just changing the wavelength of the pump laser," says Sahin Kaya Ozdemir, PhD, a research scientist in Yang's group and the first author of the paper.

Yang's team integrated Raman lasing in a silica microcavity with the mode splitting technique pioneered by her group to develop a new, powerful sensor that more readily detects nanoparticles. The technology will benefit the electronics, acoustics, biomedical, plasmonics, security and metamaterials fields.

Yang's microsensor is in a class called whispering gallery mode resonators (WGMRs) because it works similarly to the renowned whispering gallery in London's St. Paul's Cathedral, where a person on one side of the dome can hear a message spoken to the wall by another person on the other side. Yang's device does much the same thing with light frequencies rather than audible ones.

One of the main differences between early resonators and the novel resonator, known as a morphology dependent resonator, was they didn't use mirrors to reflect light. Yang's WGMR is an actual mini-laser that supports "frequency degenerate modes," patterns of excitation inside the mini-laser's doughnut-shaped ring that are of the same frequency. One portion of light beamed by the Raman laser goes counterclockwise, another goes clockwise. When a particle lands on the ring and scatters energy between these modes, the single Raman lasing line splits into two lasing lines with different frequencies.

When a Raman laser beam is generated in the resonator, it likely will encounter a particle, such as a virus nanoparticle, on the circle. When the beam initially sees the particle, the beam splits into two, generating two lasing lines that serve as reference to the other to form a self-referenced sensing technique.

"Our new sensor differs from the earlier whispering gallery sensors in that it relies on Raman gain, which is inherent in silica, thereby eliminating the need for doping the microcavity with gain media, such as rare-earth ions or optical dyes, to boost detection capability," Ozdemir says. "This new sensor retains the biocompatibility of silica and could find widespread use for sensing in biological media."

"It doesn't matter what kind of wavelength is used, once you have the Raman laser circulating inside and there is a molecule sitting on the circle, when the beam sees the particle it will scatter in all kinds of directions," Yang says. "Initially you have a counterclockwise mode, then a clockwise mode, and by analyzing the characterization of the two split modes, we confirm the detection of nanoparticles."

In addition to the demonstration of Raman microlasers for particle sensing, the team says their work shows the possibility of using intrinsic gain mechanisms, such as Raman and parametric gain, instead of optical dyes, rare-earth ions or quantum dots, for loss compensation in optical and plasmonic systems where dissipation hinders progress and limits applications.

Source: Washington University in St. Louis

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