Could Improve Tumor Imaging
Aug. 14, 2009
A new oxygen nanosensor that couples
a light-emitting dye with a biopolymer – simplifies the imaging of
oxygen-deficient regions of tumors. Such tumors are associated with
increased cancer aggressiveness and are particularly difficult to treat.
The new material
developed by Zhang and Fraser emits a long-lived phosphorescent
afterglow that is evident only under low oxygen or oxygen-free
conditions. The material may be useful for tumor imaging.
Oxygen nanosensors are powerful new research tools that one day may also
be used for the diagnosis and detection of diseases and for planning
The new material is based on poly(lactic acid), a biorenewable,
biodegradable polymer that is safe for the body and the environment, and
is easy and inexpensive to fabricate in many forms, including films,
fibers and nanoparticles. It is useful for medical research as well as
environmental research, sustainable design and green products, too.
The versatile sensor material is the result of research combining green
chemistry with nanotechnology, and is reported in the current online
edition of the journal Nature Materials.
Chemists at the University of Virginia developed the material and
consulted with cancer researchers at the U.Va. Cancer Center and Duke
University Medical Center to determine possible applications.
Guoqing Zhang, a U.Va. chemistry doctoral candidate, working with
Cassandra Fraser, a U.Va. chemistry professor, synthesized the new
material by combining a corn-based biopolymer with a dye that is both
fluorescent and phosphorescent. The phosphorescence appears as a
long-lived afterglow that is only evident under low oxygen or
Zhang devised a method to adjust the relative intensities of short-lived
blue fluorescence and long-lived yellow phosphorescence, ultimately
creating a calibrated colorful glow that allows visualization of even
minute levels of oxygen. The biomaterial displays its oxygen-sensitive
phosphorescence at room or body temperature, making it ideal for use in
"We were amazed at how easy the material was to synthesize and fabricate
as films and nanoparticles, and how useful it is for measuring low
oxygen concentrations," Fraser said.
"It is based on a bio-friendly material," added Zhang. "It is safe for
the body and the environment, and so we realized it could have
applications not just for medical research and developing improved
disease treatments, but also for new sustainable technologies."
Cancer researchers at Duke quickly realized that the new material could
be particularly useful for real-time and extended-time spatial mapping
of oxygen levels in tumors. This is important because a lack of
sufficient oxygen in tumors – called "hypoxia" – is a major source of
resistance to radiation and chemotherapy treatment, and promotes a
greater degree of malignancy.
"We have found that these nanoparticles were directly applicable to our
existing tumor models," said Greg Palmer, assistant professor of
radiation oncology at Duke University Medical Center. "This technology
will enable us to better characterize the influence of tumor hypoxia on
tumor growth and treatment response."
Researchers and clinicians have long sought effective ways to locate and
map low-oxygen areas in the body to better understand normal and disease
processes. Presently, there are no simple, easy or inexpensive methods,
preclinical or clinical, for generating oxygen maps of tumors and
surrounding tissues with good spatial and temporal resolution.
"The method developed here holds great promise for being able to perform
measurements of tumor hypoxia cost-effectively," said study co-author
Mark Dewhirst, a professor of radiation oncology, pathology and
biomedical engineering at Duke. "This kind of tool could greatly
increase our knowledge about methods to eliminate tumor hypoxia, which
could lead to more effective treatments."
"Tumors that have insufficient oxygen tend to be more likely to spread
from the primary site to other parts of the body," added Michael Weber,
director of U.Va.'s Cancer Center. "Despite the overall importance of
tumor hypoxia, it is very difficult to measure directly and most methods
that are available are very expensive."
The new material currently is being used in preclinical studies to gain
insight into cancer biology and treatment response, which could be
useful for drug development and testing.
"This technology enables entirely new insights to be obtained, allowing
imaging of tumor hypoxia on the scale of tumor cells and small blood
vessels," Palmer said.
the material could be used as an injectable nanosensor, potentially
providing continual data on oxygen levels, biological processes and
Hypoxia also is linked to cardiovascular disease, stroke and diabetes,
so the material developed by Zhang and Fraser could have applications in
several areas of medicine.
Applications for the light-emitting biomaterial beyond medicine include
molecular probes for cell biology, imaging agents for visualizing fluid
and aerodynamics, and oxygen sensors for food and drug packaging, tamper
resistant seals, and environmental monitoring, such as measuring oxygen
levels in bodies of water.
The research is funded by the U.S. National Science Foundation, the U.S.
Department of Defense, U.S. National Institutes of Health, the James and
Rebecca Craig Foundation, through the U.Va. Cancer Center, and the U.Va.