LA JOLLA, Calif. , September 10, 2002
|Erkki Ruoslahti, M.D., Ph.D.|
Researchers at The Burnham Institute and UC San Diego's Jacobs School of Engineering have developed hybrid organic/inorganic machines that home to cancerous tissues in live mice. They programmed miniature, nanocrystalline semiconductor particles, called quantum dots ("qdots"), and wrapped them with tiny pieces of protein that home to specific addresses inside living tissue ("homing peptides"). The homing peptides were developed by Erkki Ruoslahti, M.D., Ph.D., Distinguished Professor at The Burnham Institute. This accomplishment-the first successful targeting of an inorganic nanomachine into a cancerous tumor-will be published in The Proceedings of the National Academy of Sciences (PNAS), www.pnas.org, this week.
Qdots are small nanocrystals, less than 10 nm, that are extremely luminous and relatively stable. It is possible to tune the qdot's light frequency across the light spectra by altering the crystal's particle size or composition. Qdots have a relatively large surface area-to-volume ratio, which makes them a feasible platform for building more complex nanodevices in the future.
Qdots programmed to emit red or green light were injected intravenously into live mice and delivered to three different tissues. The qdot's destination was determined by its peptide coating which coded for either normal lung tissue, the blood vessels feeding tumors, or the lymphatic vessels draining tumor tissue.
Researchers have been working for many years to find a way to use nanomachines to deliver drugs, diagnose disease, or provide images of tissues in the body. Q-dots are attractive candidates for such nanotechnology because they glow, making it easy to track and see the miniscule particles. For targeting, much research has focused on the use of antibodies to help locate and bind to specific tissues, such antibodies may make the nanodevices too large to travel freely to the tumor.
The homing peptides developed by Dr. Ruoslahti are advantageous to the development of nanomedicine. The smallest of the homing peptides used in this study were comprised of 9 amino acids; a whole protein such as an antibody is huge by comparison. Two of the peptides used in this study home to the nucleus of their target, tumor cells. The investigators hope eventually to be able to direct a nanomachine all the way to the nucleus of a target cell.
Sangeeta Bhatia, Ph.D., Associate Professor of Bioengineering at the UCSD Jacobs School, says the work could lead to a revolution in the field of nanotechnology: "We are enthusiastic about these results because we showed that qdots could be successfully used inside the body without causing blood clotting, and because the homing peptides successfully directed the qdots to a specific type of cancer, in this case, breast cancer." Bhatia and her postdoctoral fellow Warren Chan developed the qdots used in the study.
The use of qdots as a prototype nanodevice, together with homing peptides as a prototype targeted delivery system, demonstrates proof of concept for developing simple robots that could be instructed to probe the bloodstream and tissues in search of disease at its earliest stages.
Research Associate Pirjo Laakkonen, Ph.D., and graduate student Maria Akerman working in Dr. Ruoslahti's laboratory contributed to this collaboration. Dr. Ruoslahti is the corresponding author of the paper reporting these results.
This research was funded by grants from the National Institutes of Health, the Department of Defense Breast Cancer Research Program, DARPA, the Susan G. Komen Breast Cancer Foundation, the David and Lucile Packard Foundation, and with fellowships awarded from the American-Scandinavian Foundation, the National Institutes of Health, the Academy of Finland and the Finnish Cultural Foundation.