Diblock copolymer micellar nanoparticles decorated with annexin-A5 proteins

Jul 17 2006

One of the banes of modern cancer therapy is that clinicians and patients must often wait months before they can tell if a given treatment is working.

This delay not only puts patients at risk, but also increases the duration of clinical trials, slowing the development of promising new therapies. To remedy this unacceptable situation, investigators have turned to nanotechnology, and two new reports suggest that they may be on the right track.

Writing in the journal Bioconjugate Chemistry, a research team led by Geralda van Tilborg, Ph.D., at the Eindhoven University of Technology, in The Netherlands, describes its advanced work developing a protein- and polymer-coated quantum dot that binds to cells undergoing apoptosis and is visible using both fluorescence spectroscopy and magnetic resonance (MR) imaging. In the meantime, investigators at the University of Bordeaux, in France, report in the Journal of the American Chemical Society on their initial work on a polymer nanoparticle that could be used to both deliver drugs to cancer cells and report that those cells are dying as a result.

In earlier work, the Dutch investigators had developed a relatively large liposomal nanoparticle for imaging apoptosis, the programmed cell death that occurs during successful anticancer therapy. In their latest work, the researchers chose quantum dots as the core nanoparticle and used it as an anchor for the protein annexin A5 and a magnetic coating. Annexin A5 is a naturally occurring protein that binds tightly to a cell membrane component called phosphatidyl serine, which is normally found only on the inside of the cell membrane. An early event that occurs during apoptosis is that the cell membrane folds inside out, making phosphatidyl serine available for binding to annexin A5. Indeed, the results presented in this current paper showed that this quantum dot agent only identified cells undergoing apoptosis.

By using quantum dots as the fluorescent core of this dual-mode imaging agent, the researchers were able to reduce the size of the nanoscale construct from 100 nanometers down to about 10 nanometers. As a result, the researchers note, this quantum dot-based agent should be able to more easily penetrate tissues and reach deeply buried tumors. The researchers also note that this apoptosis imaging agent is ready to use in animal cancer models.

Though the French team's work is not as far along, it too shows the promise of using annexin A5-coated nanoparticles to detect apoptosis. This group of investigators, led by Redouane Borsali, Ph.D., and Alain Brisson, Ph.D., have developed a method for attaching annexin A5 to self-assembling polymer nanoparticles. These nanoparticles can be loaded with anticancer agents, as well as other targeting molecules or imaging agents, and can be designed to release their targets with a change in local concentrations of calcium.

The work on a fluorescent and magnetic quantum dot apoptosis detector is detailed in a paper titled, "Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis." Investigators from the Utrecht Institute for Pharmaceutical Sciences and the University of Maastricht, both in The Netherlands, also participated in this study. An abstract of this paper is available through PubMed. View abstract.

The work using polymer nanoparticles to detect apoptosis is detailed in a paper titled, "Diblock copolymer micellar nanoparticles decorated with annexin-A5 proteins." This paper was published online in advance of print publication. An abstract is available at the journal's website. View abstract.