How nanotubes enter cells

Scientists worldwide are teasing apart the precise mechanisms behind how tubes of carbon only nanometers or billionths of a meter wide enter cells, findings that researchers could employ to help these nanotubes deliver medicines or genes into the body, experts told UPI's Nano World.

Physical chemist Hongjie Dai's team at Stanford University in California are exploring carbon nanotubes as therapeutic agents. For instance, while biological tissue is transparent to near-infrared light, carbon nanotubes absorb it, and Dai and his colleagues in August reported that by tagging carbon nanotubes so that they would specifically latch onto cancer cells and shining near-infrared lasers on them, they could kill just cancer cells without harming normal tissue.

Dai's team also showed that carbon nanotubes could carry proteins and DNA into cells potentially to help deliver drugs or therapeutic genes. Compared with a solid spherical nanoparticle, a hollow nanotube has more surface area with which to carry molecules, explained biomolecular engineer Michael Strano at the University of Illinois at Urbana-Champaign.

Dai and his colleagues wanted to pinpoint how carbon nanotubes enter cells and where they end up inside. Compounds can enter either a cell using passive mechanisms that do not consume energy, where they just pass through the cell membrane, or via active mechanisms such as endocytosis, where cells engulf a target.

Knowing the route carbon nanotubes take and their final destinations could help determine what kinds of molecular bonds researchers should use to attach compounds with, organic chemist Alberto Bianco at the Institute of Molecular and Cellular Biology at Strasbourg in France explained. For instance, endocytosis places substances inside acidic cellular compartments known as lysosomes and endosomes. If scientists know nanotubes will end up there, they can attach drugs or genes using disulfide bonds, which get cleaved within lysosomes, "and thus we can release biological cargo from the nanotube transporters," Dai said. "Disulfide bonds are widely used for in vitro delivery and are among the most efficient."

Endocytosis requires either energy in the form of the molecule ATP or warmth. Dai and his colleagues found cooling cell cultures or dosing cells with an inhibitor that stopped ATP production meant they could no longer absorb carbon nanotubes, suggesting cells take up carbon nanotubes using endocytosis. Inhibitors against a tripod-shaped protein called clathrin specifically showed that cells apparently use a clathrin-dependent endocytosis pathway to absorb the tubes. Dai's team published its findings online Dec. 8 in the international scientific journal Angewandte Chemie.

Prior research from Bianco and organic chemist Maurizio Prato at the University of Trieste in Italy, chemical engineer Kostas Kostarelos at the University of London and their colleagues, who are also investigating carbon nanotubes as delivery vehicles for drugs or genes, suggested carbon nanotubes entered cells via a mechanism other than endocytosis. Strano pointed out this discrepancy is due to the different molecules each team attached to their carbon nanotubes. While Bianco and his colleagues used positively charged peptides, Dai's team used negatively charged DNA and proteins.

Strano added that Bianco and his colleagues found their carbon nanotubes got carried into the nucleus, while Dai's team's tubes appeared to disperse more generally across the cell. "There is a lot of research to explore in both cases," Strano said. For instance, Bianco's teams tubes could be used more for gene delivery, while Dai's team's tubes might be used to heat the cell as a whole for anti-cancer strategies.

Ultimately, future research should test how effective carbon nanotubes are compared with competing nanotechnologies, Strano said. For instance, scientists have also been investigating other nanomaterials, such as hollow nanoparticles, for use in drug and gene delivery, and gold-silica nanoparticles known as nanoshells for a heat-based anti-cancer therapy similar to that Dai and colleagues proposed using carbon nanotubes.

Copyright 2005 by United Press International

Related stories:

'Nanobamas' fuse art, science, technology and politics
(PhysOrg.com) -- A University of Michigan professor has created 3-D portraits of the president-elect that are smaller than a grain of salt. He calls them "nanobamas."
Miniaturizing memory: Taking data storage to the molecular level
Computers are getting smaller and smaller. And as hand-held devices — from mobile phones and cameras to music players and laptops — get more powerful, the race is on to develop memory formats that can satisfy the ever-growing demand for information storage on tiny formats.
Tiny solar cells built to power microscopic machines
Some of the tiniest solar cells ever built have been successfully tested as a power source for even tinier microscopic machines. An article in the inaugural issue of the Journal of Renewable and Sustainable Energy (JRSE), published by the American Institute of Physics (AIP), describes an inch-long array of 20 of these cells -- each one about a quarter the size of a lowercase "o" in a standard 12-point font.
3D nanotube assembly technique for nanoscale electronics
(PhysOrg.com) -- For the past several years, researchers have been trying to take advantage of carbon nanotubes’ good electrical properties for future nanoscale electronics applications. One of the biggest challenges in this area is finding ways to arrange and assemble the nanotubes into 3D configurations for carrying current in nanoscale devices.
'Buckyballs' have high potential to accumulate in living tissue
Research at Purdue University suggests synthetic carbon molecules called fullerenes, or buckyballs, have a high potential of being accumulated in animal tissue, but the molecules also appear to break down in sunlight, perhaps reducing their possible environmental dangers.
Study Details How Platinum Nanocages 'Cook' Cancer Cells
Platinum-based anticancer agents have a long history as proven therapeutic agents, but their toxicity and short lifetime in the body and the ability of tumors to develop resistance to these drugs limit the ultimate utility of these agents.
Slipping through cell walls, nanotubes deliver high-potency punch to cancer tumors in mice
(PhysOrg.com) -- The problem with using a shotgun to kill a housefly is that even if you get the pest, you'll likely do a lot of damage to your home in the process. Hence the value of the more surgical flyswatter.
Carbon Nanotube-Coated Electrodes Improve Brain Readouts
A research group has significantly improved the quality of brain-function measurements by coating metal neural electrodes with carbon nanotubes. Their work could potentially allow scientists to learn more about brain diseases that are based on electrical impulse malfunctions, such as Parkinson's and epilepsy.

News discussion:

Nanotechnology news