Modification to Particles Could Lead to Better Surgical Imaging

Originally Published MDDI March 2004

R&D DIGEST

Erik Swain

New ways to modify the surfaces of nanoscale crystallized particles could lead to breakthroughs in cancer surgery and other procedures.

These particles, called quantum dots, are tiny fluorescent crystals that can emit light through fluorescent signals. Unlike traditional fluorescent markers, they are very bright and do not bleach if harshly illuminated. 

Until recently, quantum dots could not circulate for long in vivo, limiting their use for long-term biological studies. But a team of scientists from Quantum Dot Corp. (Hayward, CA), which owns the rights to a form of quantum dots called Qdot Particles, and Carnegie Mellon University (Pittsburgh) found a way to change that. 

First, they found that Qdot Particles coated with an amphiphilic polyacrylic acid are stable in vivo. Then, they found that if a second polymer coat is added to the surface molecules, the quantum dots circulate for a longer time in the body.

“Our findings are a promising step toward using quantum dots for non-invasive imaging in humans to monitor and treat diseases such as cancer,” said Byron Ballou, a research scientist at the Molecular Biosensor and Imaging Center at Carnegie Mellon's Mellon College of Science. “Using our modified quantum dots, we were able to non-invasively image structures in living mice by fluorescence, then prove that the quantum dots were present by electron microscopy. No other fluorescent label lets you verify its exact location on scales from the whole animal to molecular dimensions.” The findings have been published in the January/ February issue of Bioconjugate Chemistry. Funding came from the National Institutes of Health.

Further surface modifications can occur by attaching biological and non-biological molecules. This could lead to targeting tumors to image them more effectively. They could enable precise tracking of cancer cells to a sentinel lymph node (the first to which a cancer spreads), which could lead to great improvements in lymphoma surgery. They could also be used in lateral flow assays to provide a one-step diagnostic test that gives a result in minutes. Quantum Dot Corp. scientists are working on the latter project with researchers at the Jet Propulsion Laboratory (Pasadena, CA). Genotyping, DNA expression studies, and protein analysis are also potential applications.

In a recent paper in Nature Biotechnology, Roger Uren, MD, a clinical associate professor of medicine at the University of Sydney, underscored the benefits of quantum dots. They will radically improve tumor removal, he wrote, by allowing surgeons to see the target tissue clearly and remove it.

Quantum dot particles are composed of a few hundred to a few thousand items of semiconductor material, usually cadmium selenide, and emit light in a variety of colors, depending on size.

“The new coatings allowed us to observe quantum dots much longer than previously demonstrated,” said Ballou. “We had concerns that the coats might dissolve or be digested away, so we are pleased with the long persistence of fluorescence, as well as the large increase in circulating time. Both of these features enabled the quantum dots to deposit effectively within tissues.”

The modified particles have so far remained fluorescent for eight months. In the animals tested so far, they are localized mostly in the lymph nodes, liver, spleen, and bone marrow, all of which have a high concentration of immune cells called phagocytes. This suggests the quantum dots were collected by the phagocytic cells, and that the dots could be useful for identifying tumor types in these areas. 

Further testing must take place to ensure that quantum dots do not cause toxicity in healthy cells. The Carnegie Mellon researchers also plan to see if the dots can be targeted to cells other than phagocytes, and to try to modify them to create in situ biosensors that could, for example, report how a tumor is responding to therapy. 

Ballou's colleagues on the project included Lauren Ernst, Christopher Langerholm, and Allan Waggoner of Carnegie Mellon and Marcel Bruchez, principal scientist at Quantum Dot Corp.

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