There are many potent hydrophobic and amphiphilic toxins, for which no effective diagnostic tests or therapies exist, that disrupt biological systems and can lead to death. An excellent example is endotoxin [i.e. gram-negative bacterial lipopolysaccharide (LPS)]. Endotoxemia, the presence of LPS in the bloodstream of a wounded warrior for instance, can lead to septic shock which carries a high mortality. The objective of this project is to synthesize, characterize, and understand how biomimetic lipid nanoparticles (BLNs) interact with hydrophobic and amphiphilic small molecule toxins. Novel strategies like fluorescence quenching by gold nanoparticles will be used in order to develop biosensors that identify and quantify toxins in complex solutions. In addition, BLNs will be studied in relevant biosystems to demonstrate rapid toxin sequestration to inhibit devastating cell responses to toxin exposure. The Thaxton Lab has critical expertise in the synthesis of BLNs and a track record for understanding the binding of small molecules to the bionanoparticles in a way that increases our understanding of interactions at the bio-nano interface. Important for this project, the surface chemical properties of BLNs will be systematically manipulated in order to tune and optimize binding of certain toxins and inflammatory mediators, like LPS. In addition, we will demonstrate function of the materials at biotic interfaces with regard to inhibiting untoward biological consequences of exposure to biotoxins. We anticipate that this research will provide critical bionanomaterials with known structure-function relationships that can be leveraged to develop next generation sensors and toxin-specific antidotes. This is of great importance to the men and women in the US Armed Services as these types of materials could be used to detect and treat acute exposure to biowarfare toxins and exposure to amphiphilic inflammatory mediators of sepsis, like LPS, that are the source of profound morbidity and mortality.
|Effective start/end date||7/15/13 → 7/14/19|
- Air Force Office of Scientific Research (FA9550-13-1-0192)