Bee sting toxin harnessed to kill tumour cells

In collaboration with the Press Association

US scientists have isolated the toxin in bee venom and attached it to tiny nanospheres designed to target tumour cells.

These so-called 'nanobees' allow the bee toxin, melittin, to be delivered directly to the tumour so that it targets cancer cells and does not harm surrounding healthy tissue.

The toxin, which is actually a small protein, is attracted to the membranes of cells, through which it forms pores so that the cells break up and are destroyed.

It is known to be an effective antibacterial and antifungal agent as it can destroy any cell it comes into contact with, as long as it is present in high enough concentrations.

Study co-author Dr Samuel Wickline, who leads the Siteman Centre of Cancer Nanotechnology Excellence at Washington University, explained: "The nanobees fly in, land on the surface of cells and deposit their cargo of melittin which rapidly merges with the target cells.

"We've shown that the bee toxin gets taken into the cells where it pokes holes in their internal structures."

Publishing their findings in the Journal of Clinical Investigation, the researchers revealed that their nanobees were effective in mice, which received four to five injections of nanoparticles over several days.

The experimental treatment was given to mice which had been implanted with human breast cancer cells or melanoma cells to cause tumours.

Researchers found that tumour growth in mice with breast tumours slowed by nearly 25 per cent following the treatment, while the size of melanoma tumours decreased by 88 per cent compared with untreated tumours.

They then added a targeting agent so that the nanobees were attracted to growing blood vessels around tumours.

This caused the nanobees to be guided to precancerous skin lesions - which have rapidly growing blood vessels - where they reduced the proliferation of cancerous cells by 80 per cent.

The study also showed that by using nanoparticles rather than simply injecting melittin into the bloodstream, the technique prevented widespread destruction of the body's healthy cells.

Mice which received the treatment had normal blood counts and no signs of organ damage, indicating that the toxin did not cause them harm.

In addition, whereas melittin is normally cleared from the mice's circulation within minutes, it was still found to be circulating 200 minutes later when secured to nanoparticles.

The researchers claim that nanobees may be useful for slowing the growth and reducing the size of tumours, as well as for preventing cancer from progressing from its early stages.

Co-author Dr Paul Schlesinger, associate professor of cell biology and physiology, commented: "Cancer cells can adapt and develop resistance to many anticancer agents that alter gene function or target a cell's DNA, but it's hard for cells to find a way around the mechanism that melittin uses to kill.

"Nanobees are an effective way to package the useful, but potentially deadly melittin, sequestering it so that it neither harms normal cells nor gets degraded before it reaches its target."

Professor Wickline described melittin as a "workhorse" that is very stable when attached to nanoparticles, as well as being easily and cheaply produced.

"Melittin fortunately goes onto the nanoparticles very quickly and completely and remains on the nanobee until cell contact is made," he added.

Nell Barrie, science information officer at Cancer Research UK, commented: "Although there's a real buzz around using nanotechnology to treat cancer, there's still a long way to go.

"This research is an example of how nanoparticles could be used to deliver drugs directly to cancer cells without harming healthy cells. But so far this work has only been done in mice, and will need to be proven to be both safe and effective in humans before it could ever be used to treat cancer."

References

Soman, N., Baldwin, S., Hu, G., Marsh, J., Lanza, G., Heuser, J., Arbeit, J., Wickline, S., & Schlesinger, P. (2009). Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth Journal of Clinical Investigation DOI: 10.1172/JCI38842