February 21, 2006
Smaller Quantum Dots Improve In Vivo Imaging
Quantum dots, nanoscale sized semiconductor crystals, have proven themselves as brilliantly colored labels for a wide variety of biochemical studies, and have shown promise as imaging agents, particularly for mapping so-called “sentinel lymph nodes” for metastatic lesions. Now, a new type of quantum dot, smaller even than the original nanoscale ones made of cadmium selenide and zinc sulfide, could provide a means of tracking key biochemical processes in living animals, as well as act as a tool for mapping a more extensive set of lymph nodes for cancer metastases.
Reporting its work in the Journal of the American Chemical Society, a team of investigators led by Moungi Bawendi, Ph.D., of the Massachusetts Institute of Technology, describes its efforts to create a new type of quantum dot that absorbs near-infrared light. This portion of the spectrum is not absorbed by water or biomolecules, and thus, can pass a significant distance through skin. The fruits of the group’s labors is a family of quantum dots that have a core of indium selenide surrounded by a shell of zinc sulfide. The core is further coated with dihydrolipoic acid connected to a short length of poly(ethylene glycol). The dihydrolipoic acid helps the quantum dots mix easily with water, while the poly(ethylene glycol) prevents proteins in blood and serum from sticking to the quantum dots.
This last property turns out to be particularly useful because it makes the new quantum dots functionally smaller than their older cadmium selenide counterparts. Though the two types of quantum dots are close in size physically when created in the laboratory, the cadmium selenide quantum dots, as well as the new ones lacking poly(ethylene glycol), become functionally larger when mixed with biological fluids because of the large number of proteins that stick to their surfaces.
The unusually small functional size, also called the hydrodynamic diameter, of the new quantum dots yielded two new properties that the researchers note hold particular promise for biomedical applications. The researchers first observed that when they injected the new quantum dots beneath the skin of mouse or rat, the quantum dots quickly migrated to the nearest lymph nodes. Though this group and others had observed this behavior with other types of quantum dots, Bawendi and his colleagues were surprised when the new quantum dots continued migrating through the lymphatic system, allowing the investigators to image up to five lymph nodes as well as the lymphatic channels between the nodes.
The investigators received a second surprise when they injected the new quantum dots directly into the bloodstream of mice. Normally, quantum dots circulate through the bloodstream and are then excreted, but the researchers observed the new quantum dots escaping from the bloodstream and migrating toward tissues. The investigators noted in their paper that this critical behavior represents an important milestone toward the successful use of quantum dots for imaging important biomolecules in living animals.
This work, funded in part by the National Cancer Institute, is detailed in a paper titled, “Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging.” Researchers from the Beth Israel Deaconess Medicine Center in Boston and Ajou University in Yeongtong-Gu Suwon, Korea, also participated in this study. This paper was published online in advance of print publication. An abstract is available at the journal’s website.