In work that could at the same time impact the delivery of
drugs and explain a biological mystery, MIT engineers have created the
first synthetic nanoparticles that can penetrate a cell without poking
a hole in its protective membrane and killing it. The key to their
approach? Stripes.
 | | MIT researchers have created 'striped' nanoparticles capable of entering a cell without rupturing it. In the background of this cartoon are cells that have taken up nanoparticles carrying fluorescent imaging agents. Francesco Stellacci, Darrell Irvine and colleagues, MIT |
The team found that gold nanoparticles coated with alternating
bands of two different kinds of molecules can quickly pass into cells
without harming them, while those randomly coated with the same
materials cannot. The research was reported in a recent advance online
publication of Nature Materials.
"We've created the first fully synthetic material that can
pass through a cell membrane without rupturing it, and we've found that
order on the nanometer scale is necessary to provide this property,"
said Francesco Stellacci, an associate professor in the Department of
Materials Science and Engineering and co-leader of the work with
Darrell Irvine, the Eugene Bell Career Development Associate Professor
of Tissue Engineering.
In addition to the practical applications of such
nanoparticles for drug delivery and more--the MIT team used them to
deliver fluorescent imaging agents to cells--the tiny spheres could
help explain how some biological materials such as peptides are able to
enter cells.
"No one understands how these biologically derived cell-penetrating
materials work," said Irvine. "So we could use the new particles to
learn more about their biological counterparts. Could they be analogues
of the biological system?"
When a cell membrane recognizes a foreign object such as a
nanoparticle, it normally wraps around or "eats" it, encasing the
object in a smaller bubble inside the cell that can eventually be
excreted. Any drugs or other agents attached to the nanoparticle
therefore never reach the main fluid section of the cell, or cytosol,
where they could have an effect.
Such nanoparticles can also be "chaperoned" by biological
molecules into the cytosol, but this too has drawbacks. Chaperones can
work in some cells but not others, and carry one cargo but not another.
Hence the importance of the MIT work in developing
nanoparticles that can directly penetrate the cell membrane, deliver
their cargo to the cytosol, and do so without killing the cell.
Irvine compares the feat to a phenomenon kids can discover.
"If you have a soap film and you poke it with a bubble wand, you'll pop
it," he said. "But if you coat the bubble wand with soap before poking
the film, it will pass through the film without popping it because it's
coated with the same material." Stellacci notes that the coated
nanoparticles have properties similar to the cell membrane--not
identical--but the analogy is still apt.
Stellacci first reported the creation of the striped
nanoparticles in a 2004 Nature Materials paper. At the time, "we
noticed that they interacted with proteins in an interesting way," he
said. "Could they also have interesting interactions with cells?" Four
years later, he and his colleagues report a resounding "yes."
Stellacci and Irvine's coauthors are Ayush Verma, Oktay Uzun,
Ying Hu and Suelin Chen of the Department of Materials Science and
Engineering (MSE); Yuhua Hu of the Department of Chemical Engineering;
Hee-Sun Han of the Department of Chemistry, and Nicky Watson of the
Department of Biology.
Irvine has appointments in the Department of Biological
Engineering and MSE, and is a member of the David H. Koch Institute for
Integrative Cancer Research at MIT. He was recently named a Howard
Hughes Medical Institute investigator.
The research was funded in part by the NSF, the NIH and the
Packard Foundation.
Posted June 10th, 2008
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