January 8, 2007
Detecting Cell Death with Quantum Dots
By combining a quantum dot with a novel carrier of the magnetic resonance imaging (MRI) agent gadolinium, a team of investigators at the University of Maastricht, in The Netherlands, has developed a nanoparticle that can spot apoptosis, or programmed cell death, using both MRI and fluorescence imaging. Tests in animals showed that this nanoparticle can provide anatomical information using MRI and cellular level information using fluorescence imaging. Imaging programmed cell death in the body could provide an early indication that an antitumor therapy is indeed killing cancer cells.
Reporting its work in the journal Nano Letters, a research team headed by Dick Slaaf, Ph.D., Marc van Zandvoort, Ph.D., and Chris Reutelingsperger, Ph.D., first developed a biocompatible molecular structure capable of binding strongly to eight gadolinium atoms, and then linked multiple carriers to each fluorescent quantum dot. The investigators also attached one molecule of annexin A5, a molecule that binds to the surface of cells undergoing apoptosis. The resulting nanoparticle contained enough gadolinium atoms to produce a strong MRI signal that would be detectable even if only a few of the nanoparticles were able to bind to an apoptotic cell.
To test the imaging ability of this nanoparticle, the investigators added it to cells triggered to start apoptosis. During the initial stages of apoptosis, the researchers were able to detect small patches of green fluorescence on the cell membrane. As apoptosis continued, these green patches spread across the entire cell membrane.
MRI experiments showed that the nanoparticle produced an imaging signal that was approximately 40 times stronger than that produced by the gadolinium carrier alone. Subsequent imaging experiments were able to detect injury-induced apoptosis in mice.
This work is detailed in a paper titled, “Optical and magnetic resonance imaging of cell death and platelet activation using annexin A5-functionalized quantum dots.” An investigator from the Technische Universiteit Endhoven, in The Netherlands, also participated in this study. This paper was published online in advance of print publication. An abstract is available at the journal’s website.