More effective early detection of diseases is one of the promises of nanotechnology. Current imaging methods, such as x-rays and magnetic resonance imaging, are limited in the size of tumors they can detect in the depth they can penetrate the body, and by their potential side effects. Another promising imaging technique, NIR bioimaging, is a noninvasive, painless, and nonionizing form of radiation that operates at wavelengths just above that of visible light. By combining NIR imaging with nanoparticles containing an NIR fluorescing dye, indocyanine green, the researchers were able to detect 5-mm diameter breast cancer tumors in a live mouse model over a period of 4 or more days.
Indocyanine green is the only NIR organic dye approved by the FDA for use in the human body. The nanoparticles, which are around 20 nanometers in diameter, are made of calcium phosphate, a biocompatible material that has long been used as a bone replacement. Unlike other nanoparticles considered for imaging and drug delivery, the biodegradable components of calcium phosphate nanoparticles are already widely present in the bloodstream.
In addition to the combination of NIR imaging and nanoparticles, a second innovation is the development of a fundamentally new method for processing nanoparticulates. The process is called van der Waals high-performance liquid chromatography.
Materials scientist Jim Adair, Ph.D., whose team synthesized the particles, said, “Our technique takes advantage of the large van der Waals forces associated with particles, as opposed to the small van der Waals forces associated with molecules, atoms, and ions. The hard part in the synthesis was making sure the particles did not clump together. The critical stage was the laundering of all the nonessential byproducts associated with the synthesis. By the end, we had a very clean suspension of particles in which all the spectator ions, molecules, and atoms had been washed away from the basic nanoparticles.”
Dr. Adair’s group then teamed with Mark Kester, Ph.D., and his colleagues to demonstrate that their nanoparticles provide the fluorescent dye with 200-percent greater photoefficiency compared with indocynine green injected into the bloodstream, with a 500-percent greater photostability. In a separate experiment discussed in the paper, the researchers were able to image through 3 centimeters of dense pig muscle tissue, which should correlate to at least 10 centimeters, and likely much deeper, in patients, according to Dr. Adair. The investigators then injected these nanoparticles into mice with implanted human breast tumors and were able to image 5-m diameter tumors within 24 hours after injection.