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August 23, 2004
Scientists target tumors with 'quantum dots'

By holly korschun

Emory scientists have for the first time used a new class of luminescent “quantum dot” nanoparticles in living animals to simultaneously target and image cancerous tumors. Encapsulated in a highly protective polymer coating and attached to a monoclonal antibody that guides them to prostate tumor sites in living mice, the quantum dots are visible using a simple mercury lamp.

The scientists believe the ability to both target and image cells in vivo represents a significant step in the quest to use nanotechnology to target, image and treat cancer, cardiovascular plaques and neurodegenerative disease in humans. The findings appeared in the Aug. 1 edition of Nature Biotechnology.

The research team was led by Shuming Nie, a nanotechnology expert and professor in the joint Emory/Georgia Tech Coulter Department of Biomedical Engineering and the Winship Cancer Institute, and by Lelund Chung, professor of urology in the School of Medicine and Winship.

Quantum dots are nanometer-sized luminescent semiconductor crystals that have unique chemical and physical properties due to their size and highly compact structure. Quantum dots can be chemically linked (conjugated) to molecules such as antibodies, peptides, proteins or DNA and engineered to detect other molecules, such as those present on the surface of cancer cells.

The researchers injected human prostate cancer cells under the skin of mice to promote growth of solid prostate tumors. They then encapsulated quantum dots (made from cadmium selenide) within a highly protective coating called an ABC triblock copolymer, and overcoated the particle-polymer composite with poly (ethylene glycol). The dots were injected into the circulatory system of the mice first to test “passive” targeting of the tumor.

Tumors grow extra blood vessels in a process called angiogenesis. These angiogenic vessels are very porous, allowing the quantum dots to leak out and accumulate at the tumor sites, where they can be detected by fluorescence imaging.

The scientists then conjugated the quantum dots to a highly specific monoclonal antibody targeted to a prostate-specific membrane antigen on the surface of the tumor cells. When injected into the mice’s circulatory system, the conjugated dots selectively accumulated at the site of the tumor through binding to the antigen target. The new triblock polymer coating protected the quantum dots from attack by enzymes and other biomolecules. The active method of tumor targeting using the monoclonal antibody was much faster and more efficient than was the passive method without the antibody.

“Although other research groups have used quantum dots to either target or image cells, we believe this is the first time in vivo targeting and imaging has been achieved simultaneously,” said Xiaohu Gao, a postdoctoral fellow in Nie’s group.

In previous studies without using the ABC triblock polymer, Emory scientists and other researchers experienced a significant loss of fluorescence in quantum dots administered to live animals.

“This polymer appears to lend a great deal of protection and stability to the quantum dot probes inside the animals,” Gao said. “Also, cadmium and selenium ions are highly toxic, and this polymer acts like a plastic bag to protect the quantum dots from degradation and leakage.”

The research was funded by the National Institutes of Health, the Georgia Cancer Coalition, the Coulter Translational Research Program at Emory and Georgia Tech, and the Department of Defense.

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