Quantum dots (QDs) are nanoparticles of one semiconductor surrounded by a second semiconductor. There has been considerable interest in their use as inorganic fluorophores, owing to the fact that they offer significant advantages over conventionally used fluorescent markers. For example, QDs have fairly broad excitation spectra — from ultraviolet to red — that can be tuned depending on their size and composition. At the same time, QDs have narrow emission spectra, making it possible to resolve the emissions of different nanoparticles simultaneously and with minimal overlap. Last, QDs are highly resistant to degradation, and their fluorescence is remarkably stable.

In the top row, nuclear antigens and microtubules were labelled with QDs and the fluorescent dye Alexa 488, respectively. The bottom row shows the reverse combination. Continuous illumination for three minutes caused the Alexa signal to fade completely, whereas QDs remain stable during the same period. Reproduced, with permission, from Wu et al. © (2003) Macmillan Magazines Ltd.

But despite their promise, the feasibility of using QDs in biological preparations has been questioned. If the semiconductors are not perfectly coated, the fluorescent signal is quenched, making it imperative to develop appropriate coats for QDs. It is also necessary to establish ways for QDs to interact specifically with the biomolecule of interest and to reduce nonspecific binding. Last, to be used in vivo, QDs should not be toxic or interfere with cellular function. Two recent papers in Nature Biotechnology give a strong push to the use of QDs as tools for cellular imaging by reporting ways to circumvent these problems.

In the first paper, Wu et al. coated QDs with a polyacrylate cap and covalently linked them to antibodies or to streptavidin. They then used these nanoparticles to label surface, cytoskeletal and nuclear proteins in fixed cells and tissue sections. Labelling was highly specific, and was brighter and more stable than that of other fluorescent markers. Moreover, they simultaneously used two QDs of different emission spectra and managed to detect two different targets with a single excitation wavelength.

Wu et al. also succeeded in labelling live cells with their QDs, but in the second paper, Jaiswal et al. provide compelling evidence for the use of QDs in vivo. They coated the nanoparticles with dihydrolipoic acid, and electrostatically conjugated them to avidin or to antibodies through an intermediate, positively charged protein. The authors allowed cells to incorporate the QDs by endocytosis and followed their fate for more than a week. The cells continued to grow, differentiate and respond to cellular signals in a normal way. Similarly, the label was stable throughout the experiment and there was minimal nonspecific binding. Last, Jaiswal et al. also used QDs with different emission properties to show the feasibility of simultaneously detecting more than one fluorophore.

As the use of quantum dots is still in its early days, these two papers and their demonstration that QDs are viable imaging tools should stimulate their use in neurobiology, a field in which their potential has not begun to be explored yet.