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Nanotechnology Shows Early Promise to Treat Cardiovascular
Disease
A new tactic in the battle against cardiovascular
disease – employing nanoengineered molecules called
“nanolipoblockers” as frontline infantry
against harmful cholesterol – is showing promise
in early laboratory studies at Rutgers, The State University
of New Jersey.
I Rutgers researchers have proposed a way to combat
clogged arteries by attacking how bad cholesterol triggers
inflammation and causes plaque buildup at specific blood
vessel sites. Their approach contrasts with today’s
statin drug therapy, which aims to reduce the amount
of low-density lipids, or LDLs (“bad” cholesterol),
throughout the body.
In an ironic twist, the Rutgers approach aims to thwart
a biological process that is typically beneficial and
necessary. Prabhas Moghe, the principal investigator
and associate professor of biomedical engineering and
chemical and biochemical engineering at Rutgers, said
that vascular plaque and inflammation develop when certain
forms of LDL are attacked by white blood cells that
scavenge cellular debris and disease agents. “While
these scavengers, called macrophages, perform an essential
role in keeping organisms healthy, their interaction
with highly oxidized LDL molecules has quite the opposite
effect,” he said.
Moghe explains that macrophages accumulate large amounts
of oxidized LDL and secrete chemicals that can damage
the neighboring tissues and, ultimately, become fatty
foam cells. The researchers’ approach, therefore,
is to create clusters of nanoengineered molecules that
target specific receptor molecules on cell membranes
and block these oxidized LDLs from attaching to macrophages.
Moghe is working with Kathryn Uhrich, Rutgers professor
of chemistry and chemical biology, who is an expert
at synthesizing biologically useful molecules at the
nanoscale – anywhere from 10 to 100 nanometers
long. The research team, which also includes graduate
student Evangelia Chnari and synthetic chemists Lu Tian
and Jinzhong Wang, has designed a family of nanolipoblockers,
or NLBs, which compete with oxidized LDL for a macrophage’s
attention. The NLBs bind to receptor sites on macrophages,
cutting the accumulation of oxidized LDL by as much
as 75 percent.
The NLB particles are made of several engineered organic
strands or chains whose ends cluster around a central
point, creating a structure known as a micelle. Uhrich
synthesized molecule chains with several different characteristics,
such as attracting or repelling water or having a positive
or negative charge. When the chains assembled into micelles,
Moghe tested them for how well they blocked LDL uptake.
“We’re employing the tools of nanotechnology
– specifically tailoring the structure of the
molecule, changing groups on the ends of the chains
and closely analyzing which forms of the particles bind
to the different macrophage receptors,” Uhrich
said. “The significant finding of our study is
that the nanoscale organization matters tremendously
for blockage of oxidized LDL, which opens new avenues
for more specific targeting of receptors.”
Moghe said that if this method proves feasible in living
organisms, it could convey treatment to the site of
the problem, rather than a systemic approach. “While
statins are a great stride in preventing cardiovascular
disease, they are not suitable for everyone,”
Moghe said. “Our approach also has potential to
topically address the recurrence of inflammation and
blockage at stent surgery sites, something that systemically
active drugs have not been shown to consistently do.”
Research to test the performance of NLBs in living organisms
is now under way.
The study was supported by grants from the National
Science Foundation and the American Heart Association.
Visit http://ur.rutgers.edu
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