PHILADELPHIA -- Nano-sized
particles embedded with bright, light-emitting molecules
have enabled researchers to visualize a tumor more
than one centimeter below the skin surface using only
infrared light. A team of chemists, bioengineers and
medical researchers based at the University of Pennsylvania
and the University of Minnesota has lodged fluorescent
materials called porphyrins within the surface of
a polymersome, a cell-like vesicle, to image a tumor
within a living rodent. Their findings, which represent
a proof of principle for the use of emissive polymersomes
to target and visualize tumors, appear in the Feb.
7 online early edition of the Proceedings of the National
Academy of Science.
"We have shown that the
dispersion of thousands of brightly emissive multi-porphyrin
fluorophores within the polymersome membrane can be
used to optically image tissue structures deep below
the skin with the potential to go even deeper,"
said Michael J. Therien, a professor of chemistry
at Penn. "It should also be possible to use an
emissive polymersome vesicle to transport therapeutics
directly to a tumor, enabling us to actually see if
chemotherapy is really going to its intended target."
This work takes advantage of
years of effort in the Therien laboratory focused
on the design of highly fluorescent compounds. Polymersomes,
which were developed by Penn professors Daniel A.
Hammer and Dennis Discher in the mid-1990s, function
much like the bilayered membranes of living cells.
Whereas cell membranes are created from a double layer
of fatty phospholipid chains, a polymersome is comprised
of two layers of synthetic co-polymers. Like a living
cell, the polymersome membrane has a hydrophobic core.
The study shows that the fluorophores evenly disperse
within this core, giving rise to a nanometer-sized
"These polymers are also
larger than phospholipids, so that there is enough
space for the fluorophores, which are larger than
the average molecule that is found inside cell membranes,"
said Hammer, professor and chair of the Department
of Bioengineering at Penn School of Engineering and
Applied Sciences. "Another feature that makes
emissive polymersomes so useful is that they self-assemble.
Simply mixing together all component parts gives rise
to these functional nanometer-sized, cell-like vesicles."
In their study, the researchers
demonstrate how they can use these emissive polymersomes
to target markers on the surface of a specific type
of tumor cells. When exposed to near-infrared light,
which can travel through tissue, the fluorophores
within the polymersome respond with a bright near-infrared
signal that can then be detected.
"The fluorophores function
like reflectors stuck in the spokes of a bicycle tire,"
Therien said. "When this structure absorbs light,
it gives rise to an intense, localized fluorescence
signal that is uniquely suited for visualizing living
According to Therein, there
is keen interest in developing new technology that
will enable optical imaging of cancer tissue, as such
technology will be less costly and more accessible
than MRI-based methods and free of the harmful side
effects associated with radioactivity. In this imaging
system, the flourophores can also be tuned to respond
to different wavelengths of near-infrared light. This
sets the stage for using emissive polymersomes to
target multiple cancer cell-surface markers in the
Emissive polymersomes perform
much like in vivo imaging systems that use semiconductor-based
"quantum dots." These quantum dots, however,
are hard matter, which could collect within the circulatory
system, potentially causing a stroke. According to
the Penn researchers, brightly emissive polymersomes
define the first nanotech optical imaging platform
based on non-aggregating "soft matter" (polymers
and porphyrins) and hence have enormous potential
This research was supported
by a National Cancer Institute research grant to Therien
and a Biomedical Imaging and Bioengineering research
grant to Hammer and Therien.
P. Peter Ghoroghchian, a graduate
student in Penn Department of Bioengineering, was
the lead author on the study. Graduate student Paul
R. Frail and senior research associate Kimihiro Susumu,
both of Penn Department of Chemistry, designed the
emissive structures. Dana Blessington and Britton
Chance of the Department of Biochemistry and Biophysics
in Penn School of Medicine performed the live-animal
imaging experiments described in the paper. Co-authors
Aaron K. Brannan and Frank S. Bates, from the Department
of Chemical Engineering and Materials Science at the
University of Minnesota, carried out cryogenic transmission
electron microscope studies of the emissive polymersome
structures and provided design principles for the
polymers used in the study.
Contact: Greg Lester
University of Pennsylvania