Nanosponges To Suck Up Toxins

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Bacteria are becoming more resistant to the best weapon we have against them: antibiotics. But what if we could live together in peace? Instead of killing the germs, there may be a way to render them harmless to the body using nanosponges to soak up the toxins that make us sick.

Could nanosponges become the next universal antidote? Bioengineer Che-Ming "Jack" Hu of the University of California, San Diego says there is potential. Besides soaking up bacterial toxins, nanosponges theoretically could also be used against snake bites and bee stings, absorbing the venom that sends the body into toxic shock.

He and his team engineered nanometer-sized polymer particles coated in proteins that mimic those of a red blood cell membrane, that, as reported in their study published today in the journal Nature Nanotechnology, can absorb a broad class of toxins from the body.

Hu said he got the idea when he and his colleagues were looking at nanoparticles for drug delivery. "We wanted to mimic the red blood cell because they are 'privileged,'" he said. "They can go anywhere in the body."

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The toxin tested was alpha-haemolysin from staphylococcus bacteria. It damages cells because it is what is called "pore forming." The alpha-haemolysin molecules are attracted to the proteins in cell walls, and when they attach, they weaken the molecular bonds -- essentially putting holes in the cells. The cell dies, and enough of the toxin is fatal.

Developing the nanosponges in a way that attacks the pore-forming toxins, Hu says was key. "The first thing (the toxins) have to do is get through the cell membrane," Hu said.

For the nanosponges, he and his team essentially engineered a fake red blood cell; it's surface is chemically a near-match. As a result, the alpha-haemolysin molecules in the toxin are attracted to the nanosponges instead of the body's cell walls.

Since the inside of the nanosponge is a polymer, and solid, the toxic molecule just sticks there and doesn't damage living cells. At that point, the nanosponge can carry the toxin to the liver, where it gets eliminated from the body. (The alpha-haemolysin doesn't attack the liver cells because the side of the molecule that would damage them is attached to the sponge already). One nanosponge can soak up a lot of alpha-haemolysin molecules.

The nanoparticles were tested on mice that had been given lethal doses of alpha-haemolysin from MRSA. If the mice were "vaccinated" with the nanosponges 89 percent of them lived. When they were given the nanosponges after being dosed with the toxin 44 percent of them survived.

Giving the mice nanosponges and alpha-haemolysin toxin at the same time, the mice suffered no problems even when the ratio of toxin molecules to nanosponges was 70 to 1.

There is still some way to go before this kind of treatment becomes a routine part of care. "To be used in the clinic it would be important to capture the toxin very early upon infection, as the damage can occur quite quickly," said Jean-Christophe Leroux, a professor in the Institute of Pharmaceutical Studies at the Swiss Federal Institute of Technology. "It would have to be shown that this approach also works in humans which is not so obvious in this case due to the model chosen," he said. Leroux was not involved in the study.

And while the nanosponges may have the capability to cover a wide range of pore-forming toxins, this method wouldn't be as effective against something that attacks cells in a different way, such as a nerve agent.

Currently, however most antidotes to toxins aren't quite so wide-ranging: snake antivenins, for example, are often specific to certain species or families. And snake antivenin won't do any good against the poisons produced by bacterial infections.

With nanosponges designed as red blood cells, even though the venom from some snake species and the bacterial alpha-haemolysin will be different molecules, with vastly different shapes -- they work the same way, via their attraction to cell membranes.

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