Sugars Attach Nanotubes To Cells

One of the concerns about carbon nanotubes is their potential toxicity. Recent research shows that coating nanotubes with a glycopolymer that mimics cell surfaces renders the nanotubes nontoxic and could open the way to using them for a range of biological applications.

Carbohydrates on the surface of cells are the main way that cells recognize external molecules. A team of researchers led by chemistry professor Carolyn R. Bertozzi, physics professor Alex Zettl, and graduate student Xing Chen at the University of California, Berkeley, and Lawrence Berkeley National Laboratory has taken advantage of this fact to interface carbohydrate-coated carbon nanotubes with living cells through cell-surface receptors (J. Am. Chem. Soc. 2006, 128, 6292). The coated nanotubes are less toxic to cells than uncoated carbon nanotubes.

Bertozzi wants to use carbon nanotubes as sensors of the cellular environment. "Carbon nanotubes in the proximity of cells might be used to detect molecules that are secreted from the cells, changes in the molecular composition of the cell surface, or local changes in pH that relate to the cell's metabolic state," she says.

Bertozzi and Zettl's team makes the glycopolymer of a poly(methyl vinyl ketone) backbone adorned with α-N-acetylgalactosamine residues (α-GalNAc), which resemble the sugar moieties on a type of cell-surface glycoproteins known as mucins. The scientists attach the coated nanotubes to cells by using a cell-surface protein that is specific for α-GalNAc sugars—agglutinin from the snail Helix pomatia (HPA).

The team interfaced the coated nanotubes and cells through two different pathways. In the first, HPA is first attached to the coated nanotubes; in the second, to the cell surface. Both methods can connect the cells and nanotubes. "We pursued both methods in parallel because we could perform different control experiments in each pathway that confirmed that the interaction between the nanotubes and cells was mediated by the HPA-carbohydrate interaction," Bertozzi says.

Michael S. Strano, a chemical engineer at the University of Illinois, Urbana-Champaign, who also works with functionalized nanotubes, says the results are not unexpected scientifically. "The polymer is designed to stick to cell surfaces, so it is not surprising that the nanotube-polymer system does the same," he says. "The real importance of this work is that it further bolsters the case that suitably functionalized single-walled carbon nanotubes are not cytotoxic and have clear and compelling advantages when utilized in biological systems."

In the past, interactions between nanotubes and cells have been observed to be nonspecific. In contrast, this work describes "one of the first cases where nanoparticle-cell interactions are rationally controlled using specific binding to cell receptors," says Vicki Colvin, chemistry professor and director of the Center for Biological & Environmental Nanotechnology at Rice University. "If we can control and understand the interface that nanoparticles have with living systems, we can build better biotechnologies as well as create safer nanoparticles."

One of the challenges, Colvin says, is figuring out what changes actually make the nanotubes nontoxic. Some of Colvin's work has shown that it doesn't necessarily matter how the nanotubes are derivatized, just the extent to which they are. "If we can relate carbon nanotube toxicity to simple physicochemical parameters such as water solubility or degree of derivatization, it opens the door for more rational design of risk management for carbon nanotube products," she says.

At this point, the nanotubes just bind to the outside of the cells. "It remains to be carefully addressed if these types of glycopolymer-nanotube noncovalent complexes are eventually internalized by the cells, and what is the fate of the nanotubes," says Alberto Bianco, an associate researcher at the French National Center for Scientific Research in Strasbourg who has used conjugated nanotubes to deliver peptides and nucleic acids to cells.

In addition to biosensors, this approach "will enable new applications, including nanotube-based tissue engineering scaffolds that target specific cells," Strano says.