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• W2755201611 abstract "Despite intensive investigation of molecular mechanisms underlying the pathogenesis of sepsis, many aspects of sepsis remain unresolved; this hampers the development of appropriate therapeutics. In the present study, we developed a biologic nanomedicine containing a cationic antimicrobial decapeptide KSLW (KKVVFWVKFK), self-associated with biocompatible and biodegradable PEGylated phospholipid micelles (PLM), and analyzed its efficacy for treating sepsis. KSLW was modified with polyethylene glycol (PEG)-aldehyde or was conjugated with distearoylphosphatidylethanolamine (DSPE) -PEG-aldehyde. We compared the antibacterial and antiseptic effects of PEG-KSLW and PLM-KSLW with those of unmodified KSLW both in vitro and in vivo. We found that the PLM-KSLW improved the survival rate of sepsis mouse models without undesired immune responses, and inhibited lipopolysaccharide (LPS)-induced severe vascular inflammatory responses in human umbilical vein endothelial cells compared with unmodified KSLW or PEG-KSLW. Furthermore, PLM-KSLW dramatically reduced the bacterial count and inhibited bacterial growth. We also found a new role of PLM-KSLW in tightening vascular barrier integrity by binding to the glycine/tyrosine-rich domain of occludin (OCLN). Our results showed that PLM-KSLW had a more effective antiseptic effect than KSLW or PEG-KSLW, possibly because of its high affinity toward OCLN. Moreover, PLM-KSLW could be potentially used to treat severe vascular inflammatory diseases, including sepsis and septic shock." @default.
• W2755201611 created "2017-09-25" @default.
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• W2755201611 date "2017-01-01" @default.
• W2755201611 modified "2023-09-27" @default.
• W2755201611 title "Dual Functioned Pegylated Phospholipid Micelles Containing Cationic Antimicrobial Decapeptide for Treating Sepsis" @default.
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• W2755201611 doi "https://doi.org/10.7150/thno.20734" @default.
• W2755201611 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5667346" @default.
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