Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Slipping through cell walls, nanotubes deliver high-potency punch to cancer tumors in mice

19.08.2008
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.

Cancer researchers have long faced a similar situation in chemotherapy: how to get the most medication into the cells of a tumor without "spillover" of the medication adversely affecting the healthy cells in a patient's body.

Now researchers at Stanford University have addressed that problem using single-walled carbon nanotubes as delivery vehicles. The new method has enabled the researchers to get a higher proportion of a given dose of medication into the tumor cells than is possible with the "free" drug—that is, the one not bound to nanotubes—thus reducing the amount of medication that they need to inject into a subject to achieve the desired therapeutic effect.

"That means you will also have less drug reaching the normal tissue," said Hongjie Dai, professor of chemistry and senior author of a paper, which will be published in the Aug. 15 issue of Cancer Research. So not only is the medication more effective against the tumor, ounce for ounce, but it greatly reduces the side effects of the medication.

Graduate student Zhuang Liu is first author of the paper.

Dai and his colleagues worked with paclitaxel, a widely used cancer chemotherapy drug, which they employed against tumors cells of a type of breast cancer that were implanted under the skin of mice. They found that they were able to get up to 10 times as much medication into the tumor cells via the nanotubes as when the standard formulation of the drug, called Taxol®, was injected into the mice.

The tumor cells were allowed to proliferate for about two weeks prior to being treated. After 22 days of treatment, tumors in the mice treated with the paclitaxel-bearing nanotubes were on average less than half the size of those in mice treated with Taxol.

Critical to achieving those results were the size and surface structure of the nanotubes, which governed how they interacted with the walls of the blood vessels through which they circulated after being injected. Though a leaky vessel—nautical or anatomical—is rarely a good thing, in this instance the relatively leaky walls of blood vessels in the tumor tissue provided the opening that the nanotubes needed to slip into the tumor cells.

"The results are actually highly dependent on the surface chemistry," Dai said. "In other words, you don't get this result just by attaching drugs to any nanotubes."

The researchers used nanotubes that they had coated with polyethylene glycol (PEG), a common ingredient in cosmetics. The PEG they used was a form that has three little branches sprouting from a central trunk. Stuffing the trunks into the linked hexagonal rings that make up the nanotubes created a visual effect that Dai described as looking like rolled-up chicken wire with feathers sticking out all over. The homespun sounding appearance notwithstanding, the nanotubes proved to be highly effective delivery vehicles when the researchers attached the paclitaxel to the tips of the branches.

Dai's team has found in earlier work (Proceedings of the National Academy of Sciences, Vol. 105, No. 5, 1410-1415, Feb. 5, 2008) that coating nanotubes with PEG was an effective way to keep the nanotubes circulating in the bloodstream for up to 10 hours, long enough to find their way to the target location and much longer than free medication would circulate. Although attaching the paclitaxel to the PEG turned out to reduce the circulation time, it proved to still be long enough to deliver a highly effective dose inside the tumor cells.

All blood vessel walls are slightly porous, but in healthy vessels the pores are relatively small. By tinkering with the length of the nanotubes, the researchers were able to tailor the nanotubes so that they were too large to get through the holes in the walls of normal blood vessels, but still small enough to easily slip through the larger holes in the relatively leaky blood vessels in the tumor tissue.

That enabled the nanotubes to deliver their medicinal payload with tremendous efficiency, throwing a therapeutic wrench into the cellular means of reproduction and thus squelching the hitherto unrestrained proliferation of the tumor cells.

Dai said that the technique holds potential for delivering a range of medications and that it may also be possible to develop ways to channel the nanotubes to their target even more precisely.

"Right now what we are doing is so-called 'passive targeting,' which is using the leaky vasculature of the tumor," he said. "But a more active targeting would be attaching a peptide or antibody to the nanotube drug, one that will bind more specifically to the tumor, which should further enhance the treatment efficacy."

Dai's team is already at work developing more targeted approaches, and he is optimistic about the potential applications of nanotubes.

"We are definitely hoping to be able to push this to practical applications into the clinic. This is one step forward," he said. "But it will still take time to truly prove the efficacy and the safety."

The work was funded by the NIH-National Cancer Institute Center for Cancer Nanotechnology Excellence Focused on Therapeutic Response at Stanford, a Stanford Bio-X Initiative Grant, NIH-National Cancer Institute Grant and a Stanford Graduate Fellowship. Collaborators on this work included Assistant Professor Shawn Chen's group in the Stanford Department of Radiology.

Louis Bergeron | EurekAlert!
Further information:
http://www.stanford.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>