Chemists recruit anthrax to deliver cancer drugs

Bacillus anthracis bacteria have very efficient machinery for injecting toxic proteins into cells, leading to the potentially deadly infection known as anthrax. A team of MIT researchers has now hijacked that delivery system for a different purpose: administering cancer drugs.

"Anthrax toxin is a professional at delivering large enzymes into cells," says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT. "We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells."

In a paper appearing in the journal ChemBioChem, Pentelute and colleagues showed that they could use this disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. This is the first demonstration of effective delivery of antibody mimics into cells, which could allow researchers to develop new drugs for cancer and many other diseases, says Pentelute, the senior author of the paper.

Several antibody drugs have been developed to target receptors found on cancer-cell surfaces. However, the potential usefulness of this approach has been limited by the fact that it is very difficult to get proteins inside cells. This means that many potential targets have been "undruggable," Pentelute says. "Crossing the cell membrane is really challenging," he says. "One of the major bottlenecks in biotechnology is that there really doesn't exist a universal technology to deliver antibodies into cells."

For inspiration to solve this problem, Pentelute and his colleagues turned to nature. Scientists have been working for decades to understand how anthrax toxins get into cells; recently researchers have started exploring the possibility of mimicking this system to deliver small protein molecules as vaccines.