Rice University chemists have found a way to
load more than two million tiny gold particles called nanorods into a single
cancer cell. The breakthrough could speed development of cancer treatments that
would use nanorods like tiny heating elements to cook tumors from the inside.
The research appears online in Angewandte
Chemie International Edition.
“The breast cancer cells that we studied were so laden with gold
nanorods that their masses increased by an average of about 13%,” says
study leader Eugene Zubarev, associate professor of chemistry at Rice.
“Remarkably, the cells continued to function normally, even with all of
this gold inside them.”
Though the ultimate goal is to kill cancer, Zubarev says the strategy is to
deliver nontoxic particles that become deadly only when they are activated by a
laser.
The nanorods, which are about the size of a small virus, can harvest and
convert otherwise harmless light into heat. But because each nanorod radiates
miniscule heat, many are needed to kill a cell.
“Ideally, you’d like to use a low-power laser to minimize the risks to
healthy tissue, and the more particles you can load inside the cell, the lower
you can set the power level and irradiation time,” says Zubarev, an
investigator at Rice’s BioScience Research Collaborative (BRC).
Unfortunately, scientists who study gold nanorods have found it difficult to
load large numbers of particles into living cells. For starters, nanorods are
pure gold, which means they won’t dissolve in solution unless they are combined
with some kind of polymer or surfactant. The most commonly used of these is
cetyltrimethylammonium bromide, or CTAB, a soapy chemical often used in hair
conditioner.
CTAB is a key ingredient in the production of nanorods, so scientists have
often relied upon it to make nanorods soluble in water. CTAB does this job by
coating the surface of the nanorods in much the same way that soap envelopes
and dissolves droplets of grease in dishwater. CTAB-encased nanorods also have
a positive charge on their surfaces, which encourages cells to ingest them.
Unfortunately, CTAB is also toxic, which makes it problematic for biomedical
applications.
In the new research, Zubarev, Rice graduate student Leonid Vigderman, and
former graduate student Pramit Manna, now at Applied Materials Inc., describe a
method to completely replace CTAB with a closely related molecule called MTAB
that has two additional atoms attached at one end.
The additional atoms—one sulfur and one hydrogen—allow MTAB to form a
permanent chemical bond with gold nanorods. In contrast, CTAB binds more weakly
to nanorods and has a tendency to leak into surrounding media from time to
time, which is believed to be the underlying cause of CTAB-encased nanorod
toxicity.
It took Zubarev, Vigderman, and Manna several years to identify the optimal
strategy to synthesize MTAB and substitute it for CTAB on the surface of the
nanorods. In addition, they developed a purification process that can
completely remove all traces of CTAB from a solution of nanorods.
