In this study, the
researchers used monoclonal antibodies that targeted
specific sites on lymphoma cells to coat tiny
structures called carbon nanotubes. Carbon nanotubes
are very small cylinders of graphite carbon that heat
up when exposed to near-infrared light. This type of
light, invisible to the human eye, is used in TV
remote controls to switch channels and is detected by
night-vision goggles. Near-infrared light can
penetrate human tissue up to about 1½ inches.
In cultures of cancerous lymphoma cells, the
antibody-coated nanotubes attached to the cells’
surfaces. When the targeted cells were then exposed to
near-infrared light, the nanotubes heated up,
generating enough heat to essentially “cook” the cells
and kill them. Nanotubes coated with an unrelated
antibody neither bound to nor killed the tumor cells.
“Using near-infrared light for the induction of
hyperthermia is particularly attractive because living
tissues do not strongly absorb radiation in this
range,” said Dr. Ellen Vitetta, director of the Cancer
Immunobiology Center at UT Southwestern and senior
author of the study. “Once the carbon nanotubes have
bound to the tumor cells, an external source of
near-infrared light can be used to safely penetrate
normal tissues and kill the tumor cells.
“Demonstrating this specific killing was the objective
of this study. We have worked with targeted therapies
for many years, and even when this degree of
specificity can be demonstrated in a laboratory dish,
there are many hurdles to translating these new
therapies into clinical studies. We’re just beginning
to test this in mice, and although there is no
guarantee it will work, we are optimistic.”
The use of carbon nanotubes to destroy cancer cells
with heat is being explored by several research
groups, but the new study is the first to show that
both the antibody and the carbon nanotubes retained
their physical properties and their functional
abilities — binding to and killing only the targeted
cells. This was true even when the antibody-nanotube
complex was placed in a setting designed to mimic
conditions inside the human body.
Biomedical applications of nanoparticles are
increasingly attracting the attention of basic and
clinical scientists. There are, however, challenges to
successfully developing nanomedical reagents. One is
the potential that a new nanomaterial may damage
healthy cells and organisms. This requires that the
effects of nanomedical reagents on cells and organisms
be thoroughly studied to determine whether the
reagents are inherently toxic.
“There are rational approaches to detecting and
minimizing the potential for nonspecific toxicity of
the nanoparticles developed in our studies,” said Dr.
Rockford Draper, leader of the team from UT Dallas and
a professor of molecular and cell biology.
Other researchers from UT Southwestern involved in the
research were lead authors Pavitra Chakravarty, a
graduate student in biomedical engineering, and Dr.
Radu Marches, assistant professor in the Cancer
Immunobiology Center. Authors from UT Dallas' Alan G.
MacDiarmid NanoTech Institute were Dr. Inga Musselman,
Dr. Paul Pantano and graduate student Pooja Bajaj. Two
undergraduate students in UT Southwestern’s Summer
Undergraduate Research Fellowship program — Austin
Swafford from UT Dallas and Neil Zimmerman from the
Massachusetts Institute of Technology — also
participated.
The research was supported by the Cancer Immunobiology
Center at UT Southwestern, the Robert A. Welch
Foundation, the Department of Defense and the Center
for Applied Biology at UT Dallas.
Dr. Vitetta is a co-inventor on a patent describing
the techniques outlined in the study.
