Using light-harvesting nanoparticles to convert laser energy
into plasmonic nanobubbles, researchers at Rice
University, the University of Texas MD
Anderson Cancer Center, and Baylor College of
Medicine (BCM) are developing new methods to inject drugs and genetic payloads
directly into cancer cells. In tests on drug-resistant cancer cells, the
researchers found that delivering chemotherapy drugs with nanobubbles was up to
30 times more deadly to cancer cells than traditional drug treatment and
required less than one-tenth the clinical dose.
“We are delivering cancer drugs or other genetic cargo at
the single-cell level,” said Rice’s Dmitri Lapotko, a biologist and physicist
whose plasmonic nanobubble technique is the subject of four new peer-reviewed
studies, including one to be published in Biomaterials
and another published in PLoS ONE. “By avoiding healthy cells and delivering the drugs directly inside cancer
cells, we can simultaneously increase drug efficacy while lowering the dosage,”
he said.
Delivering drugs and therapies selectively so they affect
cancer cells but not healthy cells nearby is a major obstacle in drug delivery.
Sorting cancer cells from healthy cells has been successful, but it is both
time consuming and expensive. Researchers have also used nanoparticles to
target cancer cells, but nanoparticles can be taken up by healthy cells, so
attaching drugs to the nanoparticles can also kill healthy cells.
Rice’s nanobubbles are not nanoparticles; rather, they are
short-lived events. The nanobubbles are tiny pockets of air and water vapor
that are created when laser light strikes a cluster of nanoparticles and is
converted instantly into heat. The bubbles form just below the surface of
cancer cells. As the bubbles expand and burst, they briefly open small holes in
the surface of the cells and allow cancer drugs to rush inside. The same
technique can be used to deliver gene therapies and other therapeutic payloads
directly into cells.
This method, which has yet to be tested in animals, will
require more research before it might be ready for human testing, said Lapotko,
faculty fellow in biochemistry and cell biology and in physics and astronomy at
Rice.
The Biomaterials reports
selective genetic modification of human T-cells for the purpose of anticancer
cell therapy. The paper, which is co-authored by Malcolm Brenner, professor of
medicine and of pediatrics at BCM and director of BCM’s Center for Cell and
Gene Therapy, found that the method “has the potential to revolutionize drug
delivery and gene therapy in diverse applications.”
“The nanobubble injection mechanism is an entirely new
approach for drug and gene delivery,” Brenner said. “It holds great promise for
selectively targeting cancer cells that are mixed with healthy cells in the
same culture.”
Lapotko’s plasmonic nanobubbles are generated when a pulse
of laser light strikes a plasmon, a wave of electrons that sloshes back and
forth across the surface of a metal nanoparticle. By matching the wavelength of
the laser to that of the plasmon, and dialing in just the right amount of laser
energy, Lapotko’s team can ensure that nanobubbles form only around clusters of
nanoparticles in cancer cells.
Using the technique to get drugs through a cancer cell’s
protective outer wall, or cell membrane, can dramatically improve the drug’s
ability to kill the cancer cell, as shown by Lapotko and MD Anderson’s Xiangwei
Wu in two recent studies, one in Biomaterials
in February and another in Advanced
Materials in March.
“Overcoming drug resistance represents one of the major
challenges in cancer treatment,” said Wu. “Targeting plasmonic nanobubbles to
cancer cells has the potential to enhance drug delivery and cancer-cell
killing.”
To form the nanobubbles, the researchers must first get the
gold nanoclusters inside the cancer cells. The scientists do this by tagging
individual gold nanoparticles with an antibody that binds to the surface of the
cancer cell. Cells ingest the gold nanoparticles and sequester them together in
tiny pockets just below their surfaces.
While a few gold nanoparticles are taken up by healthy
cells, the cancer cells take up far more, and the selectivity of the procedure
owes to the fact that the minimum threshold of laser energy needed to form a
nanobubble in a cancer cell is too low to form a nanobubble in a healthy cell.
Source: Rice University