In a recent experiment, Peter Ghoroghchian, a graduate student in the Department of Bioengineering at the University of Pennsylvania, embedded fluorescent materials called porphyrins into the membrane of a polymersome. After injecting these emissive polymersomes directly into a tumor one centimeter beneath the surface of the skin of a mouse, he exposed the mouse to near-infrared light. The porphyrins emitted near-infrared signals detectable at the skin surface. The bright light-emitting molecules enabled a team of researchers from the University of Pennsylvania and the University of Minnesota to image the tumor.

“These nanoscale assemblies [polymersomes] can generate the intense, highly localized near-infrared signals needed to penetrate dense tumor tissue in a live animal,” says Dr. Michael Therien, professor of chemistry at the University of Pennsylvania, and co-principal investigator on the project. “In contrast to hard matter-based optical imaging agents, robust, near-infrared emissive polymersomes are ideally suited to impact a wide-range of medical applications.”

"Cancer cells possess unique chemical markers on their surfaces," says Therien. "Cancer or inflammatory cells can be selectively imaged by attaching chemical compounds to emissive polymersomes that bind to chemical markers on surfaces of these cells. Because the amplitude of the emissive signal emanating from targeted near-infrared-emissive polymersomes is directly related to the number of cancer cells present, this optically-based imaging approach provides the physician with quantitative information impossible to obtain with techniques such as magnetic resonance imaging." This project would aid in detecting small tumors or dormant or latent metastases that involve only a small number of cells.

To improve tumor staging and classification, the researchers are developing polymersomes that characterize how a tumor changes over time. By formulating fluorophores to emit at different wavelengths, the researchers can create a family of polymersomes that target various receptors on a tumor’s surface. "These receptors provide an index of how the tumor has mutated or evolved," says Hammer. A clearer picture of the developing tumor "would allow a clinician to determine the best line of treatment for that particular strain of tumor," he adds.

New Polymersome Possibilities

Also in development are polymersomes that would deliver chemotherapy agents directly to a tumor. The surface of the polymersomes would carry a molecule that would bind to tumor cells, its membrane would disperse fluorophores for optical imaging, with the chemotherapy "payload" carried in the interior. Currently, researchers are designing a mechanism that would allow an external stimulus, such as exposure to light or a sudden change in temperature, to destroy the polymersome membrane, releasing the therapeutic drug.

If successful, this approach would allow clinicians to deliver chemotherapy in a much more targeted manner: Optical imaging would allow them to confirm that polymersomes have reached and bound to the target tumor, while the external stimulus would trigger release of the chemotherapy agent directly to the tumor.

These synthetic but biocompatible nanoparticles offer a new mode of transport for optical imaging agents as well as an improved method of disease surveillance. "We’re excited about near-infrared-emissive polymersomes because they are so incredibly versatile," says Hammer. "Their material properties can be designed for the specific task for which they’re going to be used. We think this represents a new paradigm that will be applicable to many different medical applications."

Funding for the research was provided by the National Institute of Biomedical Imaging and Bioengineering.

Reference:

Ghoroghchian P et al., Near-infrared-emissive polymersomes: Self-assembled soft matter for in vivo optical imaging, Proceedings of the National Academy of Sciences, 102, 2922-2927, 2005.