Write your abstract here.Bacteria ferry
nanoparticles into cells for early diagnosis,
treatment.
July 7th,
2007. Researchers
at Purdue University have shown that common bacteria can deliver a
valuable cargo of “smart
nanoparticles” into a cell to precisely
position sensors, drugs or DNA for the early diagnosis and
treatment of
various diseases.
The
approach represents a potential way to overcome hurdles in delivering
cargo to the interiors of cells, where they could be used as an
alterative technology for gene therapy, said Rashid Bashir, a
researcher at Purdue’s Birck Nanotechnology Center.
Caption: This
graphic depicts bacteria laden with “smart nanoparticles,” which could
carry genes, drugs, nanosensors or other cargo into the interior of
cells. Researchers at Purdue University have shown that the
nanoparticles could be used to precisely position cargo inside cells
for the early diagnosis and treatment of cancer and other diseases. The
green and red spheres represent drug-carrying polystyrene nanoparticles
of varying sizes.
Credit: Purdue University, Discovery Park
The
researchers attached nanoparticles to the outside of bacteria and
linked DNA to the nanoparticles. Then the nanoparticle-laden bacteria
transported the DNA to the nuclei of cells, causing the cells to
produce a fluorescent protein that glowed green. The same method could
be used to deliver drugs, genes or other cargo into cells.
“The
released cargo is designed to be transported to different locations in
the cells to carry out disease detection and treatment simultaneously,”
said Bashir, a professor in the Weldon School of Biomedical Engineering
and the School of Electrical and Computer Engineering. “Because the
bacteria and nanoparticle material can be selected from many choices,
this is a delivery system that can be tailored to the characteristics
of the receiving cells. It can deliver diagnostic or therapeutic cargo
effectively for a wide range of needs.”
Harmless
strains of bacteria could be used as vehicles, harnessing bacteria’s
natural ability to penetrate cells and their nuclei, Bashir said.
“For
gene therapy, a big obstacle has been finding ways to transport the
therapeutic DNA molecule through the nuclear membrane and into the
nucleus,” he said. “Only when it is in the nucleus can the DNA produce
proteins that perform specific functions and correct genetic disease
conditions.”
When
the cargo-carrying bacteria attach to the recipient cell they are
engulfed by its outer membrane, forming “vesicles,” or tiny spheres
that are drawn into the cell’s interior. Once inside the cell, the
bacteria dissolve the vesicle membrane and release the cargo.
The
method might be used to take images of diseased tissues by inserting a
cargo of fluorescent molecules into tumors that are ordinarily too
small to be detected, said Demir Akin, a research assistant professor
of biomedical engineering who specializes in nanomedicine.
“These
bacteria can potentially deliver specific molecules into a variety of
cells,” said Akin, the first author of a research paper appearing
online this week in the journal Nature Nanotechnology.
Experiments
were carried out in cultures of human cancer cells, including
intestinal, oral, liver, ovarian and breast cancer cells. The
researchers also tested their method on live mice and showed how the
technique could be used to deliver specific genes to various organs,
including the liver and kidneys.
“The
cells in the organs receiving the bacteria with nanoparticles made the
intended therapeutic proteins and emitted a light similar to a
firefly’s glow,” Akin said.
Certain
bacteria are naturally programmed to dissolve vesicle membranes, a
critical step to delivering the cargo. The nanoparticles are referred
to as “smart” because they release their cargo at precisely the right
moment after entering the cell.
“At
the same time thatthe bacteria are breaking up this vesicle membrane,
the cargo dislodges from the bacteria, which are both crucial steps in
delivering this cargo,” Akin said.
The
nanoparticles, which range in size from 40 to 200 nanometers - or
billionths of a meter - are attached to the bacteria with “linker
molecules.”
“The
use of commercially available polystyrene nanoparticles makes this
delivery system much simpler to implement than previous alternatives,”
Bashir said.
This new delivery system also is more efficient than other experimental techniques using viruses and bacteria.
“With
other techniques, you can usually incorporate only one copy of your
gene cargo to each bacterium or virus particle,” Akin said.
In
the new approach, bacteria can carry hundreds of nanoparticles, each of
which can in turn carry hundreds of drug molecules, depending on the
size of the nanoparticles.
The
approach also could make it possible to insert relatively large
structures, such as sensors and hollow filaments called carbon
nanotubes, into the interiors of cells.
The
sensors could make it possible to monitor activities inside a single
cell for the early detection of cancer and other diseases and to
monitor the progress of disease and response to drug therapy. The
carbon nanotubes could be delivered into diseased cells and then
exposed to light, causing them to heat up and kill only those diseased
cells, Akin said.
Source: Purdue University