March 20, 2006
Nanoparticles Detect Apoptosis
Apoptosis, or programmed cell death, is a hallmark effect triggered by effective anticancer drugs. Now, researchers in Korea have developed a biocompatible, fluorescent nanoparticle that could provide an early sign that apoptosis is occurring as a result of anticancer therapy. The results of their work, published in the Journal of the American Chemical Society, could provide a boost for both clinical oncology and cancer research.
The availability of a real-time assay of apoptosis would provide a critically useful tool for oncologists, who would then have the means to determine if a given therapeutic approach was working soon after that therapy was started. Cancer drug development would also benefit from a real-time apoptosis assay if such an assay could be used to provide rapid and sensitive results in high-throughput drug screening experiments.
A research team headed by Ick Chan Kwon, Ph.D., of the Korea Institute of Science and Technology, in Seoul, created their apoptosis-detecting nanoparticle by linking a fluorescent dye to a biocompatible polymer known as PEI-DOCA, which is made from branched poly(ethyleneimine), or PEI, and deoxycholic acid, or DOCA. The fluorescent dye, known as Cy5.5-DEVD, is widely used in cell biology experiments to study apoptosis. This dye is unique in that it only fluoresces when it is activated by one of two enzymes, both of which are produced by cells during the earliest stages of apoptosis.
Experiments with the resulting nanoparticles, which are some 80 to 100 nanometers in diameter, found that the nanoparticles are taken up rapidly by cells. Those cells that are undergoing apoptosis, either during nanoparticle uptake or after uptake is complete, fluoresce brightly. In contrast, normally growing cells show no fluorescence.
The investigators note that these nanoparticles should prove useful in cell-based high-throughput screens for chemicals that trigger apoptosis. Because the dye used in these nanoparticles fluoresces in the near-infrared region of the spectrum, it may also be possible to use these nanoparticles for detecting apoptosis in live animals, perhaps even humans. Near-infrared radiation is not absorbed by the body, and thus, can be detected either through the skin or using fiber optic fluorescence detectors.
This work is detailed in a paper titled, “Cell-permeable and biocompatible polymeric nanoparticles for apoptosis imaging.” Investigators from Kyungpook National University and Yonsei University, both in 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.