Anthrax, a potentially fatal disease caused by the Bacillus anthracis bacterium, infamous for being used as a biological weapon inside letters in 2001, is back - but scientists have now managed to turn it into a non-toxic, efficient drug delivery platform.
“Anthrax toxin is a professional at delivering large enzymes into cells," Bradley Pentelute, a chemist at the Massachusetts Institute of Technology (MIT) in the US and senior author of the paper, told Anne Trafton for an MIT story on the discovery. "We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells."
Now the scientists have successfully shown that they can do just that, and their research is published in ChemBioChem.
In the study, Pentelute and his team showed that they could use a “disarmed” version of the anthrax toxin to deliver two cancer-killing proteins known as antibody mimics into cells. These antibody mimics are important because they disrupt specific proteins inside cancer cells and are therefore capable of destroying them, but until now scientists haven’t been able to work out how to get them into cells.
This is the first demonstration of an effective antibody mimic delivery system, and it could allow research to develop new drugs for cancer and a range of other diseases, Pentelute explains in the MIT release.
Antibodies are proteins that are produced by our immune system to bind to pathogens, and in recent decades, scientists have designed their own antibodies that can disrupt proteins such as the HER2 receptor found on the surface of some cancer cells. Researchers have already developed a drug designed to bind to the HER2 receptor, called Herceptin, and it’s being successfully used to treat breast cancer tumours.
But the big hurdle in antibody drug research is that many of the potential drug targets are inside the cell - and scientists haven’t worked out how to get the antibody drugs there, until now.
The MIT team managed to successfully target several proteins inside cancer cells, including Bcr-Abl, which causes chronic myeloid leukaemia. The cancer cells that had the antibody mimics injected into them by the anthrax toxin underwent programmed cell suicide.
The researchers also managed to use anthrax to block a protein called hRAf-1 that’s overactive in many cancers.
"This work represents a prominent advance in the drug-delivery field," Jennifer Cochran, a bioengineer at Stanford University in the US who wasn’t involved in the study, told Trafton for MIT. "Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated."
The MIT researchers are now testing the anthrax delivery method in mice and investigating ways they can target particular cell types.