Nanoparticles may find a new use as an antidote for the 4.5 million people who are bitten each year by snakes and bees. The team of researchers led by Jeffrey O’Brien in Kenneth Shea’s lab at the University of California, Irvine used a directed evolution method to create a library of nanoparticles that could soak up and effectively deactivate snake and bee venom from human serum. Their results are reported in the Journal of the American Chemical Society this month.
The nanoparticles were assembled from a variety of small polymers that had abilities for binding various chemicals, and optimized the combinations over two generations of trial nanoparticles to find the recipe that worked best. Their best particle, dubbed “NP 2_12” (for generation 2, formulation 12), was essentially able to completely stop the potent snake and bee venom PLA2 from destroying red blood cells in a test tube. They showed that the particles absorbed the venom, and appeared to have preferentially soaked it up compared to a host of other serum proteins. Furthermore, once the particles bound the PLA2, they held on tightly. The researchers hypothesize the reason for this to be that the particles acquire a layer of proteins and mimic the natural binding substrate of the venom.
This research is important because current methods to make antidotes for venoms are time consuming and low yield. Essentially, small, nontoxic amounts of venom are injected into horses, whose immune systems recognize and produce antibodies that can specifically bind and deactivate them. These antibodies are then painstakingly purified from the blood to be turned into antidotes for human use. Antidotes must be produced specifically for each species of snake. On top of all of this, the solution has to then be refrigerated – a nontrivial problem when the majority of lethal snake bites occur in rural South and Southeast Asia. So if these nanoparticles work, they could provide a cheap and easy way to make broad-spectrum antivenoms, where a few formulations could be combined to soak up the majority of types of venom encountered, and stored without refrigeration. The team will next conduct antivenom studies in animals to assess the technology’s real-world applicability. Given their track record of making synthetic antidotes work in animals in the past, they’re expecting good results.
Article in Journal of the American Chemical Society: Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules…