Nanoconjugates as intracorporeal neutralizers of bacterial endotoxins.
Sepsis is a leading cause of mortality that is most often provoked by endotoxins (i.e. lipopolysaccharides; LPS) released by Gram-negative bacteria into the patient's bloodstream during infection. The therapeutic armory currently available for sepsis treatment is poor. We previously identified an LPS-neutralizing small molecule, PTD7. Here we tested the efficacy of novel PTD7-nanoconjugates in a murine model of sepsis. We found that PTD7-based nanoconjugates treated mice had improved survival that it was correlated with a marked decrease in proinflammatory cytokines in the blood. This proves that nanoconjugate-based endotoxin neutralizers can function as intracorporeal neutralizers of bacterial endotoxins.
Vicent
María J
MJ
Polymer Therapeutics Lab., Department of Medicinal Chemistry, Centro de Investigación Príncipe Felipe, Av. Autopista del Saler 16, E-46012 Valencia, Spain. mjvicent@cipf.es
Cascales
Laura
L
Carbajo
Rodrigo J
RJ
Cortés
Nuria
N
Messeguer
Angel
A
Pérez Payá
Enrique
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival; D006090:Gram-Negative Bacteria / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D034444:Peptoids / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D018805:Sepsis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D034444:Peptoids; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols