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Nanosponge able to neutralize toxins by destroying the cells through puncturing the cell membranes.


"Nanosponge" able to neutralize toxins by destroying the cells through puncturing the cell membranes.

The “nanosponges” are wrapped in red blood cell membranes to prevent them from being attacked by the body’s immune system.  “This is a new way to remove toxins from the bloodstream,” Liangfang Zhang, a nanoengineering professor at the UCSD Jacobs School of Engineering, said in the release. 
The “nanosponges” are free of toxins, thus safe for medical professionals to deliver general treatment versus multiple toxin-dependent treatments.

nanosponge    nanosponge_2

Left-to-Right: Engineers at the University of California, San Diego have invented a "nanosponge" capable of safely removing a broad class of dangerous toxins from the bloodstream, including toxins produced by MRSA, E. Coli, poisonous snakes and bees. The nanosponges are made of a biocompatible polymer core wrapped in a natural red blood cell membrane. Transmission electron microscopy demonstrated that the nanosponges are approximately 85 nanometers in diameter.

The researchers are aiming 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. Hu, now a post-doctoral researcher in Zhang’s lab, earned his Ph.D. in bioengineering from UC San Diego in 2011. 
Nanosponges as Decoys
In order to evade the immune system and remain in circulation in the bloodstream, the nanosponges are wrapped in red blood cell membranes. This red blood cell cloaking technology was developed in Liangfang Zhang’s lab at UC San Diego. The researchers previously demonstrated that nanoparticles disguised as red blood cells could be used to deliver cancer-fighting drugs directly to a tumor. Zhang also has a faculty appointment at the UC San Diego Moores Cancer Center.
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.
The nanosponges look like red blood cells, and therefore serve as red blood cell decoys that collect the toxins. The nanosponges absorb damaging toxins and divert them away from their cellular targets. The nanosponges had a half-life of 40 hours in the researchers’ experiments in mice. Eventually the liver safely metabolized both the nanosponges and the sequestered toxins, with the liver incurring no discernible damage.
Each nanosponge has a diameter of approximately 85 nanometers and is made of a biocompatible polymer core wrapped in segments of red blood cells membranes.
Zhang’s team separates the red blood cells from a small sample of blood using a centrifuge and then puts the cells into a solution that causes them to swell and burst, releasing hemoglobin and leaving RBC skins behind. The skins are then mixed with the ball-shaped nanoparticles until they are coated with a red blood cell membrane.


Test-tube experiments using red blood cells from mice demonstrated that the nanosponges (right image) effectively neutralized pore-forming toxins, leaving the RBCs undamaged. By comparison, RBCs mixed with toxins, but not the nanosponges, suffered damage (Left image).

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, this army of nanosponges floods the bloodstream, outnumbering red blood cells and intercepting toxins. Based on test-tube experiments, the number of toxins each nanosponge could absorb depended on the toxin. For example, approximately 85 alpha-haemolysin toxin produced by MRSA, 30 stretpolysin-O toxins and 850 melittin monomoers, which are part of bee venom.
In mice, administering nanosponges and alpha-haemolysin toxin simultaneously at a toxin-to-nanosponge ratio of 70:1 neutralized the toxins and caused no discernible damage.
One next step, the researchers say, is to pursue clinical trials.
The research was funded by the National Science Foundation (DMR-1216461) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095168).


University of California

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