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Camouflaged Nano-Soldiers Battling Micro-Enemies
Despite the discovery of new antibiotics, bacteria are becoming more and more antibiotic resistant. Most pathogenic strains have developed multi drug resistant mechanisms, making them increasingly difficult to destroy using available antibiotics. One such bacterial species is Methicillin-resistant Staphylococcus aureus, commonly known as MRSA, which poses a significant threat to public health. However, there may be an ideal antidote for this malady, scientists believe.

A recent study conducted by a group of researchers at the University of California, San Diego, reveals the possibility of using nano-sized agents to disarm microbial pathogens, such as MRSA, instead of killing them. This is accomplished using ‘nanosponges’ that absorb and neutralise the Pore-Forming Toxins (PFTs) produced by these bacteria. In an article published in the journal Nature Nanotechnology, April 2013, Professor Liangfang Zhang and the colleagues described the potential of using nanosponges for removing PFTs from the blood stream. They have successfully produced a “toxin absorbing nanosponge” by camouflaging a nanopolymer in red blood cell (RBC) membranes. Once injected into the blood, these fake red blood cells bind non-specifically to PFTs and deactivate them.

Pore-forming Toxins represent one of the most common weapons employed by the bacterial pathogens such as Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, Bacillus anthracis, Streptococcus pyogenes and Streptococcus pneumoniae. These toxins form holes in the cell membranes of the hosts, thus allowing the ions and molecules inside the cell to flow out and water from the surrounding tissues to flow in. This causes the cell to lose its functionality and eventually results in cell death. Not only pathogenic bacteria, but also some animals such scorpions, snakes and bees also produce PFTs. Over 80 different types PFTs have been discovered so far and the variations in their molecular structure demand for specific treatments for individual toxins. However, this study demonstrated that these new toxin absorbing nanosponges can be used as broad spectrum anti-toxins against a wide variety of PFTs. Bacterial toxins extracted from S. aureus and S. pyogenes as well as a Pore Forming Toxin found in bee venom was used in this study and the nanosponges were shown to be effective against all the PFTs regardless of their origin.

These toxin absorbing nanosponges were produced by incorporating poly (lactic-co-glycolicacid)(PLGA) particles into vesicles of bilayered RBC membranes including both lipids and the surface proteins. The RBC membrane coating surrounding the nanopolymer mainly serves two purposes. First, it prevents the host immune system from destroying the nanopolymer. Since the nanosponge is disguised in a natural red blood cell membrane, the host immune system doesn’t identify it as an invader. It also makes the nanosponge a RBC look-alike and baits the toxin molecules into attaching to its surface. The nanopolymer core captures the toxin molecules, keeping them away from other cellular targets. It also stabilises the RBC membrane coating, enabling the nanosponge to survive longer in the circulation system, thereby increasing the efficacy of the nanosponge. The detained toxin molecules are detoxified and accumulated in the liver where they are eventually metabolised.

Here's a video that explains how these nanosponges work:

The researchers say that they are focusing mainly on using this new discovery for finding a treatment for MRSA infections. So far, the studies have been carried out using mouse models and further clinical investigations are required to be done in order to determine their performance within human systems.

Major drawback of these anti-venom nanosponges is that, although effective against PFTs, they cannot be used as a cure for diseases caused by other types of toxins such as neurotoxins. But their potential of functioning as universal antidote is certainly an advantage. Furthermore, owing to their minute size, these nanoparticles can freely circulate through the blood stream, consequently arresting a large number of toxin molecules.

Apart from being used as anti-toxins, nanosponges can be used in numerous applications such as cleaning up organic and inorganic spills in water, purification of drinking water, oxygen delivery system, drug carriers etc. In a previous study, a research team lead by Professor Liangfang Zhang studied the possibility of cloaking nanosponges in RBC skins for using them as vehicles for systemic drug delivery.

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