Nanoparticles Medicinal to Tumors

Nanoparticles Medicinal to Tumors



   
April 2007 -   A nanotechnology 
research team has created biodegradable lifesaving particles 
that can deliver medicine deep into the lungs or infiltrate 
cancer cells while leaving normal ones alone. 
Only 100 to 300 nanometers wide - more than 100 times thinner 
than a human hair - the nanoparticles can be loaded with 
medicines or imaging agents, like gold, that will enhance the 
detection capabilities of medical tests such as CT scans and 
MRIs. 
"The intersection of materials science and chemistry is 
allowing advances that were never before possible," said 
Robert Prud'homme, a Princeton chemical engineering professor 
and the director of the team of scientists at Princeton, the 
University of Minnesota and Iowa State University funded by 
the National Science Foundation. 
He said, "No one had a good route to incorporate drugs and 
imaging agents in nanoparticles," which are particles measured 
in billionths of meters. 
Robert Prud'homme, a Princeton chemical engineering professor 
and director of Princeton's program in engineering biology. He 
is on the faculty of the Princeton Institute for the Science 
and Technology of Materials. 
Prud'homme will present the team's research April 11 in a talk 
titled "How Size Matters in the Retention of Nanomaterials in 
Tissue," to be given at the National Academy of Sciences 
meeting on Nanomaterials in Biology and Medicine in 
Washington, DC. 
The new technique, called Flash NanoPrecipitation, allows the 
researchers to mix drugs and materials that encapsulate them. 
Similar mixing techniques have been used to create bulkier 
pharmaceutical products and have proven practical on a 
commercial scale. 
The Princeton-led team, which includes chemical engineering 
professors Yannis Kevrekidis and Athanassios Panagiotopoulos, 
is the first to apply the technology to the creation of 
nanoparticles. 
The nanoparticles are too large to pass through the membrane 
of normal cells, but will pass through larger defects in the 
capillaries in rapidly growing solid tumors, Prud'homme said. 
Particles in this size range also could improve the delivery 
of inhaled drugs because they are large enough to remain in 
the lungs, but too small to trigger the body's lung-clearing 
Defense systems, he said. This trait could maximize the 
effectiveness of inhaled, needle-free vaccination systems. 
Prud'homme's research group is part of a Grand Challenges in 
Global Health research project led by David Edwards of Harvard 
University and funded by the Bill and Melinda Gates Foundation 
to develop nanoparticle-based aerosol vaccines for 
tuberculosis and diphtheria. 
David Edwards of Harvard University 
"Professor Prud'homme and his group have developed novel 
nanoparticle systems that are particularly attractive for 
applications in the developing world" because of their 
potential for use on a large scale at relatively low cost, 
Edwards said. 
The success of NanoPrecipitation depends on the fact that some 
molecules are hydrophobic, or water-fearing, while others are 
hydrophilic, or water-loving. 
Hydrophobic substances, such as oil, do not mix well with 
water. Many pharmaceutical compounds, including many current 
cancer treatments, are hydrophobic, making it difficult to 
deliver the medications through the bloodstream, given its 
high concentration of water. 
In NanoPrecipitation, two streams of liquid are directed 
toward one another in a confined area. The first stream 
consists of an organic solvent that contains the medicines and 
imaging agents, as well as long-chain molecules called 
polymers. The polymer chain is like a necklace of pearls with 
half of the pearls being hydrophopic and the other half being 
hydrophilic. The second stream of liquid contains pure water. 
When the streams collide, the hydrophobic medicines, metal 
imaging agents and polymers precipitate out of solution in an 
attempt to avoid the water molecules. 
The polymers immediately self-assemble onto the drug and 
imaging agent cluster to form a coating with the hydrophobic 
portion attached to the nanoparticle core and the hydrophilic 
portion stretching out into the water. 
By adjusting the concentrations of the substances, as well as 
the mixing speed, the researchers are able to control the 
sizes of the nanoparticles. 
The stretched hydrophilic polymer layer keeps the particles 
from clumping together and prevents recognition by the immune 
system so that the particles can circulate through the 
bloodstream. 
The hydrophobic interior of the particles environment newsures that they 
are not immediately degraded by watery environments, though 
water molecules will, over time, break the particles apart, 
dispersing the medicine. 
Ideally, the particles would persist for six to 16 hours after 
they were administered intravenously, Prud'homme said, which 
would theoretically allow enough time for the potent packages 
to slip into the solid tumor cells they encountered throughout 
the body. 
In the lab, this is precisely the amount of time it takes for 
water molecules to work their way into the centers of the 
nanoparticles and degrade them. 
The team made their particles even more resistant to early 
degradation by attaching hydrophobic substances, including 
fat-soluable vitamin E, to the medicines and imaging agents 
before incorporating them into the particles. 
Further studies of the controlled release technique currently 
are under way. 
Prud'homme's technique is essentially the opposite of previous 
techniques for improving drug delivery, which is to attach 
molecules to drugs to make them more water soluble. "Our 
advance is to use this technique and turn it around so the 
drugs stay inside our particles until we want them to leave," 
he said. 
Beyond using size alone to target cancer cells, the team is 
working with Princeton mechanical and aerospace engineering 
professor Wole Soboyejo to create nanoparticles that have 
specific linking molecules on their surfaces. These particles 
will bond to substances that are more prevalent in cancer 
cells than in normal ones. 
In addition to the Princeton group, principal investigators in 
the NSF-funded team include Christopher Macosko, professor of 
chemical engineering and materials science at the University 
of Minnesota, and Rodney Fox and Glenn Murphy, professors of 
chemical and biological engineering at Iowa State University. 

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