When they are prepared, QDs have a layer of organic ligands coating their surface, and this accounts for their hydrophobic nature. Various attempts have been made to make them water soluble by replacing these ligands with others that have a hydrophilic end, but this often degrades the optical properties of the QD. Even when this does not happen the resulting nanoparticles may, in vivo, bind non-specifically to macromolecules as well as being toxic.

What authors Benoit Dubertret, who is currently based at the CNRS & ESPCI Laboratoire d’Optique Physique in Paris, and David Norris, of the Department of Chemical Engineering and Materials Science at the University of Minnesota, have done is to put the QDs inside micelles, and this revolutionary approach now enables them to be used in biological imaging. The two researchers and their colleagues encapsulated cadmium selenide/zinc sulfide QDs in micelles made from poly(ethylene glycol)/phosphatidylethanolamine (PEG-PE) and phosphatidylcholine. The resulting entities were comparable to naturally occurring carriers like lipoproteins and viruses, which have been used for drug delivery and diagnostic imaging. What makes the encapsulated QDs particularly attractive is their regular spherical structure and size (10-15nm), as shown by transmission electron microscopy; they also repel other biomolecules so these don’t interfere.

Dubertret and Norris found that the micelles are not distorted even when the QD had a diameter above 3nm, when it fills the micelle core; indeed, it provides support for the micelle itself. This was shown with 4nm QDs whose micelles were stable for months, even in a 1M salt solution, in which empty micelles degrade and form aggregates after only a few days.

The QD-micelles could be attached to DNA by replacing some of the polymers used to form the micelle with an amino PEG-PE polymer. After in vitro experiments with this material were successful, it was used in vivo on early-stage embryos of Xenopus, the African clawed frog whose embryos were once widely used in human pregnancy testing. Several important observations resulted from this work. The QD-micelles were found to remain within the cell into which they were injected; they were non-toxic and inactive; they remained stable; and they could be used to label all embryonic cell types. The fluorescence was visible very early during development and it did not suffer photo-bleaching, which can be a problem with other markers. This last point was verified by exposing them under the microscope for 80 minutes to constant illumination at 450 nm (blue light), and the intensity remained unchanged.

"Micelle-encapsulated QDs fulfill the promise of fluorescent semiconductor nano-crystals for both in vivo and in vitro studies," says Dubertret. "Our work proposes a novel method to make semiconductor nanocrystals water soluble. Previous methods were based on a ligand-exchange strategy, whereas ours is based on the encapsulation of QD. This approach is very general and can be used for many nanometer-sized particles as long as they have a hydrophobic surface." Currently Dubertret is working on the development of QD for biotechnological and biological applications.