Wednesday, 4 September 2013

Rice researchers use Bismuth to track stem cells

Bismuth  (Bi) is a chemical element best known as being the active ingredient of a popular stomach-settling elixir and for other medical and cosmetics applications.

Today, researchers at Rice University - led by chemist Lon Wilson - announced that they are inserting bismuth compounds into single-walled carbon nanotubes to make a more effective contrast agent for computed tomography (CT) scanners, which in turn allows them to track stem cells or any other type of cells they want.

This is not the first time bismuth has been tested for CT scans, and Wilson's lab has been experimenting for years with nanotube-based contrast agents for magnetic resonance imaging (MRI) scanners. However, this is the first time anyone has combined bismuth with nanotubes to image individual cells, said Wilson.

"At some point, we realised no one has ever tracked stem cells, or any other cells that we can find, by CT. So we thought if we put bismuth inside the nanotubes and the nanotubes inside stem cells, we might be able to track them in vivo in real time." said Wilson.

In their experiments, the RICE team used pig bone marrow-derived mesenchymal stem cells and found that the bismuth-filled nanotubes, which they call Bi@US-tubes, produced CT images far brighter than those from common iodine-based contrast agents.

"Bismuth has been thought of before as a CT contrast agent, but putting it in nanotube capsules allows us to get them inside cells in high concentrations. That lets us take an X-ray image of the cell." said Wilson.

The capsules are made from a chemical process that cuts and purifies the nanotubes. When the tubes and bismuth chloride are mixed in a solution, they combine over time to form Bi@US-tubes.

The nanotube capsules are between 20 and 80 nanometres long and about 1.4 nanometres in diameter. 

"They're small enough to diffuse into the cell, where they then aggregate into a clump about 300 nanometres in diameter. We think the surfactant used to suspend them in biological media is stripped off when they pass through the cell membrane. The nanotubes are lipophilic, so when they find each other in the cell they stick together." said Wilson.

Wilson added his team's studies showed that stem cells readily absorb Bi@US-tubes without affecting their function. 

"The cells adjust over time to the incorporation of these chunks of carbon and then they go about their business. Bismuth is a heavy element, down near the bottom of the periodic table, and more effective at diffracting X-rays than almost anything else you could use. Once the bismuth is encapsulated in the nanotubes, the agent can produce high contrast in very small concentrations. The nanotube surfaces can be modified to improve bio-compatibility and their ability to target certain types of cells. They can also be modified for use with MRI, positron emission tomography and electron paramagnetic resonance imaging systems." he said. 

The Rice lab is working to double the amount of bismuth in each nanotube.

"Bismuth ions appear to get into the nanotubes by capillary action, and we think we can improve on the process to at least double the contrast, maybe more. Then we would like to combine both bismuth and gadolinium into one nanotube to produce a bimodal contrast agent that can be tracked with both MRI and CT scanners." Wilson concluded.

Eladio J. Rivera, Lesa A. Tran, Mayra Hernández-Rivera, Diana Yoon, Antonios G. Mikos, Irene A. Rusakova, Benjamin Y. Cheong, Maria da Graça Cabreira-Hansen, James T. Willerson, Emerson C. Perin, Lon J. Wilson. (2013). Bismuth@US-tubes as a potential contrast agent for X-ray imaging applications Journal of Materials Chemistry B : 10.1039/C3TB20742K

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