TRAIL encapsulated to polypeptide-crosslinked nanogel exhibits increased anti-inflammatory activities in Klebsiella pneumoniae-induced sepsis treatment.
Bacterial infections are often treated inadequately. Sepsis, being one of its most severe forms, is a multi-layered, life-threatening syndrome induced by rampant immune responses, like cytokine storms, that leads to high morbidity and death of infected patients. Particularly, the current increment in resistant bacterial strains and the lack of creative antibiotics to counter such menace are central reasons to the worsening of the situation. To avoid the said crisis, the antimicrobial peptides (AMPs) were used to target cell wall components, such as lipopolysaccharides (LPS), seems to have the most promise. These combine the ability of broad-spectrum bactericidal activity with low potential for induction of resistance. Inhibition of cytokine storms induced by activated immune cells has been considered a feasible treatment for in sepsis. One of the therapeutic approaches widely utilized in inducing apoptosis in inflammatory cells is the use of tumor necrosis factor (TNF)-related apoptosis-inducing ligands (TRAIL), which trigger an extrinsic apoptotic pathway via death receptors. Herein, we report TRAIL encapsulated in a bactericidal polypeptide-crosslinked nanogel that suppressed Klebsiella pneumoniae infection and overactive macrophages. Of interest, nanogel and TRAIL-nanogel treatments were more toxic towards LPS-activated cells than to naïve cells in cell viability assays. Treatment with TRAIL-nanogel significantly prolonged survival in septic mice and reduced bacterial numbers in circulation. As such, TRAIL-nanogel may be promising as a therapeutic agent for treating bacteria-infected diseases.
['Chen|Yu-Fon|YF|', 'Chen|Guan-Yu|GY|', 'Chang|Chien-Hsiang|CH|', 'Su|Yu-Chu|YC|', 'Chen|Yi-Cheng|YC|', 'Jiang|Yi-Sheng|YS|', 'Jan|Jeng-Shiung|JS|']
D000818:Animals D000900:Anti-Bacterial Agents D000893:Anti-Inflammatory Agents D017209:Apoptosis D003432:Cross-Linking Reagents D016207:Cytokines D006801:Humans D057446:Hydrodynamics D018836:Inflammation Mediators D007668:Kidney D007711:Klebsiella pneumoniae D008070:Lipopolysaccharides D008168:Lung D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D000080385:Nanogels D010316:Particle Size D010455:Peptides D011092:Polyethylene Glycols D011094:Polyethyleneimine D066244:Proton Magnetic Resonance Spectroscopy D000067996:RAW 264.7 Cells D018805:Sepsis D055672:Static Electricity D016019:Survival Analysis D053221:TNF-Related Apoptosis-Inducing Ligand
Nanogel Sepsis Antimicrobial peptide TNF-related apoptosis-inducing ligand