Researchers from the University of California, San Diego, US have invented ‘nanosponges’ that can absorb a range of toxins caused by MRSA and E.coli bacteria.
These nanosponges, which have been studied in mice, soak up ‘pore-forming toxins’, which destroy cells by poking holes in their cell membranes. Unlike other anti-toxin platforms that need to be custom synthesised for individual toxin type, these nanosponges can absorb different pore-forming toxins regardless of their molecular structures.
In a study against alpha-haemolysin toxin from MRSA, inoculation with nanosponges enabled 89% of mice to survive lethal doses. Administering nanosponges after the lethal dose led to 44% survival.
The team, led by nanoengineers at the UC San Diego Jacobs School of Engineering, published the findings in Nature Nanotechnology on 14 April.
‘This is a new way to remove toxins from the bloodstream,’ said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering and the senior author on the study.
‘Instead of creating specific treatments for individual toxins, we are developing a platform that can neutralise toxins caused by a wide range of pathogens, including MRSA and other antibiotic resistant bacteria,’ said Zhang.
The work could also lead to non-species-specific therapies for venomous snake bites and bee stings.
Instead of creating specific treatments for individual toxins, we are developing a platform that can neutralise toxins caused by a wide range of pathogens, including MRSA and other antibiotic resistant bacteria
The researchers aim to translate this work into approved therapies. ‘One of the first applications we are aiming for would be an anti-virulence treatment for MRSA. That’s why we studied one of the most virulent toxins from MRSA in our experiments,’ said ‘Jack’ Che-Ming Hu, the first author on the paper.
To evade the immune system and remain in circulation in the bloodstream, Zhang and his team wrapped the nanosponges in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells could be used to deliver cancer drugs directly to a tumour.
Red blood cells are one of the primary targets of pore-forming toxins. When a group of toxins all puncture the same cell, forming a pore, uncontrolled ions rush in and the cell dies.
Transmission Electron Microscopy (TEM)
The nanosponges look like red blood cells, and therefore serve as red blood cell decoys that collect the toxins. They absorb toxins and divert them away from their cellular targets. The nanosponges had a half-life of 40 hours in the experiments in mice. Eventually the liver safely metabolised both the nanosponges and the sequestered toxins, with the liver incurring no discernible damage.
Each nanosponge has a diameter of approximately 85nm and is made of a biocompatible polymer core wrapped in segments of red blood cells membranes.
Zhang’s team separated the red blood cells from a small sample of blood using a centrifuge and then put them into a solution that caused them to swell and burst, releasing haemoglobin and leaving RBC skins behind. The skins were then mixed with the ball-shaped nanoparticles until they were coated with a red blood cell membrane.
Just one red blood cell membrane can make thousands of nanosponges, which are 3,000 times smaller than a red blood cell. With a single dose, the nanosponges flood the blood stream, outnumbering red blood cells and intercepting toxins.
The researchers say the next step will be to carry out clinical trials.