Bacteria place nanoparticles in cells to aid diagnosis or treatment
18 June 2007
The natural infection mechanism of bacteria can be used to
deliver nanoparticles carrying drugs, DNA or sensors into cells for precise
diagnosis or treatment of disease.
The new approach was developed by
researchers at Purdue University in the USA. It is 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, according to
Rashid Bashir, a researcher at Purdue's Birck Nanotechnology Center.
developing the technique, the researchers attached nanoparticles to the
outside of bacteria and linked the DNA for a fluorescent protein 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."
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.
One application of the technique is to detect and
precisely locate tumours. It could insert fluorescent molecules into tumours
that are ordinarily too small to be detected, said Demir Akin, a research
assistant professor of biomedical engineering who specializes in
"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
"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
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.
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.