A new material developed at the University
of Virginia - an 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.
Oxygen nanosensors are powerful new research tools that one day may also be
used for the diagnosis and detection of diseases and for planning treatment
strategies.
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 oxygen-free conditions.
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 tissues.
"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.
Eventually the material could be used as an injectable nanosensor, potentially
providing continual data on oxygen levels, biological processes and therapy
responsiveness.
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.
Posted August 10th, 2009
