Biomimetic Nanoparticles for the Treatment of Sepsis
- 技术优势
- Eliminates LPS from bloodSpecifically targets aggressive immune responseWorks at lower concentrations to scavenge LPSEasy to synthesize on a large scale
- 详细技术说明
- Synthetic high density lipoprotein (HDL)-likenanoparticles (NPs) that effectively decrease Toll-like receptor 4 (TLR4)signaling for the treatment of bacterial sepsis. #Therapeutic #nanoparticles #anti-inflammatory#sepsis
- *Abstract
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Northwestern scientists have created synthetic nanoparticlesthat target the suppression of inflammatory cytokine secretion to overcome thebody’s aggressive immune response to sepsis. Lipopolysaccharides (LPS) are essentialcomponents of the outer cell wall of gram-negative bacteria. LPS are highly potent compoundsthat are released during bacterial infection and are the cause of significantmorbidity and mortality. Host cell recognition of LPS is mediated byTLR4 which also plays a critical role in the innate immune system. Despite itsvital role in host defense against pathogens, excessive or prolonged TLR4signaling induced by LPS leads to the release of inflammatory cytokines and hasbeen linked to a variety of pathological conditions, including septic shock,atherosclerosis, and the progression of cancer. Current drugs do not specifically target the aggressive immune response toLPS endotoxemia. Instead, clinicians rely on antibiotics to eradicate thebacterial infection and treat the symptoms of sepsis by securing the airway,correcting hypoxemia and administering fluids. There has not yet been an approach toeliminate LPS, which are still capable of inducing a severe immune responsewhen detached from the bacterium and after the infection has been cleared.Therefore, effective sepsis treatment options are still lacking. Northwestern researchers have developed a suite of biocompatible NPsthat closely mimics the size, shape, surface chemistry, and cholesterol-bindingproperties of the natural cholesterol-carrier HDL. The NPs are stable and bind to bacterialLPS. HDL-like NPs are well toleratedafter repeated IV administration without significant side effects. Initial studies show that one HDL-like NP wasparticularly effective at decreasing TLR4 signaling caused by addition ofpurified LPS or Gram-negative bacteria to model human cell lines or primaryhuman peripheral blood cells. Data showsthat 50 nM NP was sufficient to largely suppress the secretion of inflammatorycytokines TNFa, IL-1a, IL-1b, IL-6, IL-8, CCL5 and GM-CSF elicited by LPS. The LPS concentrationsemployed in these experiments were above LPS levels that are usually observedin sepsis patients, suggesting that our HDL NPs could be highly effective inscavenging and detoxifying LPS during bacterial sepsis.
- *Publications
- Foit Land Thaxton C (2015) Biomimetic lipid nanoparticles as treatment for bacterialsepsis. Journal of Immunology, 194: 122.6.
- 国家/地区
- 美国
