Bismuth-Carrying Nanotubes Show Potential for CT Imaging

Scientists have found a way to capture bismuth in a nanotube cage to tag stem cells for X-ray tracking.

Bismuth is perhaps best known as the active element in a popular stomach-settling medicine and is used in medical applications and cosmetics. Chemist Dr. Lon Wilson and his colleagues are inserting bismuth compounds into single-walled carbon nanotubes to make a more effective contrast agent for computed tomography (CT) scanners.

The study conducted by Rice University’s (Houston, TX, USA) chemist Dr. Lon Wilson and collaborators at the University of Houston (TX, USA), St. Luke’s Episcopal Hospital (Houston, TX, USA), and the Texas Heart Institute (Houston, USA) was published in the Journal of Materials Chemistry B. This is not the first time bismuth has been studied for CT scans, and Dr. Wilson’s lab has been experimenting for years with nanotube-based contrast agents for magnetic resonance imaging (MRI) scanners. But this is the first time anyone has combined bismuth with nanotubes to image individual cells, he said.

“At some point, we realized no one has ever tracked stem cells, or any other cells that we can find, by CT,” Dr. Wilson stated. “CT is much faster, cheaper, and more convenient, and the instrumentation is much more widespread [than MRI]. 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.”

Recent research validates their hypothesis. In tests using pig bone marrow-derived mesenchymal stem cells, Dr. Wilson and lead author Dr. Eladio Rivera, a former postdoctoral researcher at Rice, found that the bismuth-filled nanotubes, which they call Bi@US-tubes, produce CT images far brighter than those from typical 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,” Dr. Wilson said. “That lets us take an X-ray image of the cell.”

The capsules are synthesized 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-nm long and about 1.4-nm in diameter. “They’re small enough to diffuse into the cell, where they then aggregate into a clump about 300 nanometers in diameter,” Dr. Wilson stated. “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.”

Dr. Wilson reported that his team’s studies showed 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,” he said.

Bi@US-tubes have distinct advantages over typically used iodine-based contrast agents, according to Dr. Wilson. “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,” he said.

The agent can generate high contrast in very small concentrations once the bismuth is encapsulated in the nanotubes. The nanotube surfaces can be modified to improve biocompatibility and their capability to target specific types of cells. They can also be adapted for use with MRI, positron emission tomography (PET), and electron paramagnetic resonance imaging systems.

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,” Dr. Wilson concluded. “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.”

Related Links:
Rice University
University of Houston
Texas Heart Institute