Liu Jun,Ding Hui,Zhao Mingjie,Tu Fan,He Tian,Zhang Lizhu,Jing Yanfei,Rui Xiaohong,Zhang Shiliang
Sepsis is a systemic inflammatory response syndrome caused by infection, with high incidence and mortality. Therefore, it is necessary to carry out an effective anti-infection treatment. In this work, we designed and synthesized red blood cell (RBC) membrane-coated PLGA nanoparticles named γ3-RBCNPs, which target the highly expressed intercellular adhesion molecule-1 (ICAM-1) at the site of infection through the γ3 peptide on its surface and kill the Klebsiella pneumoniae through ciprofloxacin encapsulated in its core. In addition, the homogenous RBC membrane coated on the surface of the nanoparticles helps them avoid immune surveillance and prolong the circulation time of the drug in the body. We found that the γ3-RBCNPs target human umbilical vein endothelial cells (HUVECs) activated by TNF-α in vitro and the infected lung of mice in the sepsis model very well. In vitro evaluation suggested that γ3-RBCNPs have a low risk of acute hemolysis and are less likely to be engulfed by macrophages. In vivo evaluation showed that γ3-RBCNPs has a long half-life and good bio-safety. More importantly, we confirmed that γ3-RBCNPs have the good antibacterial and anti-infection ability in vivo and in vitro. Our research provides a new strategy for the nano-drug treatment of Klebsiella pneumoniae-induced sepsis.
Yang Yang,Yuan Ding,Bo Fan,Yi Wang,Zhengwei Mao,Weilin Wang,Jindan Wu
Sepsis is a complex disorder with very high morbidity and mortality; it can occur when an immune disorder triggers an invasion of pathogens in the host. Although many potential anti-infective and immunosuppressive treatments have been reported, we still do not have effective means of treating sepsis in clinic. The aim of this study is to develop a nanomaterial system that targets the site of inflammation and carries a combination of multiple drugs to better treat sepsis and alleviate its symptoms. We selected poly(lactide- co -glycolide acid) (PLGA) with good biocompatibility and degradability to prepare the nanoparticles (NPs) loaded with broad-spectrum antibiotic Sparfloxacin (SFX) and anti-inflammatory immunosuppressant Tacrolimus (TAC) by an emulsion-solvent evaporation method. The targeting ability of the NPs toward inflammatory sites is endowed by grafting of the γ3 peptide (NNQKIVNLKEKVAQLEA) that can specifically bind to the intercellular adhesion molecule-1 (ICAM-1), which is highly expressed on the surface of inflammatory endothelial cells. The drug loaded γ3-PLGA NPs have excellent cytocompatibility, low hemolysis ratio, and systemic toxicity. The drug loaded γ3-PLGA NPs also have excellent antibacterial property to both Gram-positive and Gram-negative bacteria and can effectively reduce the inflammation and immune response in acute lung infection mice. This study provides a simple and robust nanoplatform to treat lung infection induced sepsis, which may pave a way to design multifunctional nanomedicine for clinical translation.
危险品化学品经营许可证（带存储）