A team of researchers, led by scientists at Case Western Reserve University, has developed a multifunctional nanoparticle that enables magnetic resonance imaging (MRI) to pinpoint blood vessel plaques caused by atherosclerosis.
The technology is a step toward creating a non-invasive method of identifying plaques vulnerable to rupture–the cause of heart attack and stroke—in time for treatment.
Currently, doctors can identify only blood vessels that are narrowing due to plaque accumulation. A doctor makes an incision and slips a catheter inside a blood vessel in the arm, groin or neck. The catheter emits a dye that enables X-rays to show the narrowing.
However, Case Western Reserve researchers report online today in the journal Nano Letters that a nanoparticle built from a rod-shaped virus commonly found on tobacco locates and illuminates plaque in arteries more effectively and with a tiny fraction of the dye.
More importantly, the work shows that the tailored nanoparticles home in on plaque biomarkers. That opens the possibility that particles can be programmed to identify vulnerable plaques from stable, something untargeted dyes alone cannot.
"From a chemist's point of view, it's still challenging to make nanoparticles that are not spherical, but non-spherical materials are advantageous for medical applications" said Nicole F. Steinmetz, assistant professor of biomedical engineering at Case Western Reserve. "Nature is way ahead of us. We're harvesting nature's methods to turn them into something useful in medicine."
The rod-shaped nanoparticles are made from tobacco mosaic virus, tiny tubular organisms that infect plant cells but are benign outside the plant.
Steinmetz, a specialist in bioengineering plant viruses, teamed with Xin Yu, a professor of biomedical engineering, who specializes in developing MRI techniques to investigate cardiovascular diseases. They created a device that transports and concentrates imaging agents on plaques.
The research team includes: Michael A. Bruckman, a postdoctoral researcher, and Lauren N. Randolph, an undergraduate student, in the Steinmetz lab; Kai Jiang, a PhD student in Yu's lab; and Leonard G. Luyt, assistant professor, and Emily J. Simpson, a PhD candidate, both at department of chemistry at Western University, in London, Ontario.
Elongated nanoparticles have a higher probability of being pushed out of the central blood flow and targeting the vessel wall compared to spheres. Further the shape allows more stable attachment to the plaque, the researchers said.
The virus surface is modified to carry short chains of amino acids, called peptides, that make the virus stick where plaques are developing or already exist. Luyt and Simpson synthesized the peptides.
"The binding allows the particle to stay on the site longer, whereas the sheer force is more likely to wash away a sphere, due to its high curvature," said Yu, an appointee of the Case School of Engineering.
The virus surface was also modified to carry near-infrared dyes used for optical scanning, and gadolinium ions (which are linked with organic molecules, to reduce toxicity of the metal) used as an MRI contrasting agent. They used optical scans to verify the MRI results.
By loading the surface with gadolinium ions instead of injecting them and letting them flow freely in the blood stream, the nanoparticle increases the relaxivity—or contrast from healthy tissue—by more than four orders of magnitude.
"The agent injected in the blood stream has a relaxivity of 5, and our nanoparticles a relaxivity of 35,000," said Steinmetz who was appointed by the Case Western Reserve School of Medicine.
That's because the nanorod carries up to 2,000 molecules of the contrast agent, concentrating them at the plaque sites. Secondly, attaching the contrast agent to a nanoparticle scaffold reduces its molecular tumbling rates and leads to additional relaxivity benefit, the researchers explained.
While the view is better, they are able to use 400 times less of the contrast agent because it's delivered directly to plaques.
The tobacco virus-based nanoparticle, they said, offers another advantage: Most nanoparticles that have been developed to carry contrast agents are based on synthetic materials, some of which may stay in the body a while.
The tobacco virus is made of protein, which the body is well equipped to handle and flush from the system rapidly.
Steinmetz and Yu, members of the Case Center for Imaging Research, are now proposing to take the work a step further. They want to tailor the nanoparticles to show doctors whether the plaques are stable and require no treatment, or are vulnerable to rupture and require treatment. A rupture sets off the cascade of events that lead to heart attack and stroke.
To do this, they must first find different biomarkers of stable versus vulnerable plaques and coat the nanoparticles with different peptides and contrast agents that enable the MRI to tell one from the other.
"Our understanding of vulnerable plaques is incomplete, but once we can diagnose vulnerable plaques from stable plaques, it will be a paradigm shift in diagnosis and prognosis," Yu said.
In addition to using the technology to find vulnerabilities, it may also useful for delivering medicines and monitoring treatment, the researchers say.
Kevin Mayhood | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences