Nanosponge mops up mrsa toxin in bloodstream

Nanosponge mops up mrsa toxin in bloodstream

Scientists in the US have developed tiny sponges made from nanoparticles disguised as red blood cells that can soak up a broad range of dangerous toxins in the blood, such as from bacteria like MRSA and E. coli, and even snake and bee venom. They suggest their technology, which so far has been shown to work in mice, offers a new way to remove toxins caused by a wide range of pathogens.

The team, from the Department of NanoEngineering and Moores Cancer Centre at the University of California (UC), San Diego, reports its findings in the 14 April online issue of the journal Nature Nanotechnology.

Nanoengineering concerns itself with manipulating bits of material that are so small, they are measured in nanometers, or one billionth of a metre (10 the minus 9 meters). It would take a million or so bits of material measured in nanometers to cover the head of a pin.

In this case, the "nanosponges" the researchers developed have a diameter of approximately 85 nanometers and are made of a biocompatible polymer core wrapped in segments of red blood cells membranes.

Senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering, says in a press statement that their nanosponges offer a new way to remove toxins from the bloodstream:

"Instead of creating specific treatments for individual toxins, we are developing a platform that can neutralize toxins caused by a wide range of pathogens, including MRSA and other antibiotic resistant bacteria."

Zhang and colleagues also suggest their work could lead to non-species-specific treatments for poisonous snake bites and bee stings. This would make it more likely that people at risk and the professionals who treat them will have life-saving therapies available when they need them most.

Nanosponges Destroy Range of Pore-Forming Toxins, Eg from MRSA

The nanosponges are capable of destroying "pore-forming toxins", that is agents that destroy cells by poking holes in their membranes.

Since they can absorb different pore-forming toxins, regardless of their molecular make-up, they offer a significant advantage over other anti-toxin technologies that require each toxin type to have its own custom-made anti-toxin, says the team.

For the study, Zhang and colleagues tested how well their nanosponges dealt with alpha-haemolysin toxin from MRSA in mice.

Pre-injecting the mice with the nanosponges enabled 89% of them to survive lethal doses of the toxin. Giving them the injection after the lethal dose resulted in 44% survival.

The team is aiming to develop approved therapies using their approach. One of the first applications they want to develop is a treatment for MRSA, which is why they chose to study one of the most virulent toxins the drug-resistant bacterium produces.

Nanosponges Covered in Red Blood Cell Membrane

One of the first types of cell that pore-forming toxins attack once they get in the body is red blood cells. When a group of toxins punctures the same cell it forms a pore into which rushes an uncontrolled flow of ions, as a result of which the cell dies.

Being covered in red blood cell membrane the nansponges look like red blood cells and serve as decoys to collect the toxins. The sponges absorb the damaging toxins, thus diverting them from their cellular targets.

To cover the nanosponges in red blood cell membranes or skins, the team first separated the red blood cells from a small sample of blood in a centrifuge and then put them in a solution that causes them to swell and burst. This releases the hemoglobin and leaves the red blood cell skins behind.

They then mixed the red blood cell skins with the ball-shaped nanosponges until they became coated with red blood cell membrane.

Because of the scales involved, just one blood cell membrane has enough skin to cover many thousands of nanosponges (the sponges are about 3,000 smaller than a red blood cell).

Nanosponges Disguised As Red Blood Cells Evade Immune System

Another benefit of covering the nanosponges in red blood cell membranes is they can survive a while in the bloodstream before being attacked by the immune system.

In a previous study, the team had already shown how nanoparticles disguised as red blood cells could be used to deliver cancer drugs directly to tumors.

In this study, the nansponges had a half-life of 40 hours in the mice's bloodstream. Eventually, both the nanosponges and their captured toxic loads were safely broken down in the liver, with no detectable damage.

Each Nanosponge Mops Up a Lot of Toxic Molecules

Just one dose of the nanosponges is enough to flood the bloodstream, outnumber red blood cells and intercept the toxins.

Experimenting with the sponges in test tubes, the team found that each nanosponge could absorb quite a few molecules of each toxin, depending on the toxin.

For instance, a single nanosponge can mop up around 85 molecules of the alpha-haemolysin toxin that MRSA produces, or 30 stretpolysin-O toxins or 850 melittin monomoers, both toxins in bee venom.

In mice, the researchers found injecting nanosponges and alpha-haemolysin toxin together in a ratio of 1 nanosponge to every 70 molecules of toxin, neutralized the toxin and caused no detectable damage.

The team now wants to test the nanosponges in clinical trials.

Funds from the National Science Foundation, the National Institute of Diabetes and the Digestive and Kidney Diseases helped finance the study.

Nanoengineering is a rapidly expanding field that is creating materials with remarkably varied and new properties, and with huge potential in many sectors, ranging from healthcare to construction and electronics. In medicine, nanotechnology promises to revolutionize drug delivery, gene therapy, diagnostics, and many areas of research, development and as this study shows, clinical application.

Scientists also believe nanoscience and nanotechnology could help brain activity mapping do for the brain what the Human Genome Project did for genetics.

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Section Issues On Medicine: Medical practice