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Quantum dots are highly regarded for their superior photostability, narrow emission spectra and multitude of colors as compared to organic dyes; hence, they are increasingly being used for biological imaging applications. Lipid vesicles are commonly used for delivering molecules—from DNA to drugs—into cells. Their properties can be easily tuned to facilitate different uptake mechanisms, from adsorption to fusion to endocytosis.

So why not put these two powerful technologies together? That is just what Horst Vogel and his colleagues at the Swiss Federal Institute of Technology in Lausanne decided to do. They discovered that hydrophobic quantum dots could be stably incorporated into a lipid bilayer, offering a new way to image lipid vesicles. “High-resolution confocal imaging can now be performed for hours on model membrane systems,” explains Vogel, owing to the photostability of quantum dots. These lipid–quantum dot hybrid vesicles could be readily formed from any class of lipids and in a variety of sizes.

They did not stop there, however. Curious as to whether the hybrid vesicles could be used for nanobiotechnology applications, they made two hybrid vesicle constructs: one designed for transfer into cells (Construct I), and one designed to fuse with the plasma membrane (Construct II; Fig. 1). Their lipid compositions were almost identical, except for the addition of a very small percentage of PEG-lipid molecules, which appears to prevent the internalization of Construct II vesicles.

Figure 1: The interaction of Constructs I and II with living cells.
figure 1

Quantum dots, red; nanocontainer cargo, orange. Reprinted with permission from Angewandte Chemie International Edition.

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The Construct I hybrid vesicles are internalized by a fairly well-established transfection process; the fluorescent vesicles were observed in cells only seconds after the start of incubation. “We believe, if one would endow the Construct I hybrid vesicles with specific receptor molecules, it should be possible to target them to specific cellular organelles,” says Vogel. Notably, the lipid-coated quantum dots did not appear to have substantial cytotoxic effects.

The Construct II hybrid vesicles, serving as 'nanocontainers,' can be filled with water-soluble cargo for delivery inside the cells. Even more interestingly, when the Construct II vesicles fuse with the plasma membrane of a live cell, the quantum dots integrate into the membrane. “Combining the delivery followed by membrane staining is, for instance, helpful for monitoring the events happening at the cell membrane while the cargo is inside,” explains Vogel. The researchers filled the nanocontainers with calcium chloride and incubated them with cells loaded with a fluorescent calcium indicator, to demonstrate that both an intracellular increase in calcium and quantum dot membrane staining could be imaged.

Vogel and his colleagues are quite excited about the nanobiotechnology applications that may become possible by using this intriguing method. For example, magnetic nanoparticles carried in the lipid bilayer of the hybrid vesicles could be delivered to cell membranes. Vogel explains that then by applying an external magnetic field, this could allow “cell sorting, selective isolation of plasma membranes, selective and local manipulation of certain microdomains within the plasma membrane where quantum dots would preferentially be inserted and thereby influence cellular signaling reactions, and the manipulation and isolation of cellular organelles.”