Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis

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...

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Main Authors: Jun Liu, Hui Ding, Mingjie Zhao, Fan Tu, Tian He, Lizhu Zhang, Yanfei Jing, Xiaohong Rui, Shiliang Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2022.901979/full
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author Jun Liu
Hui Ding
Mingjie Zhao
Fan Tu
Tian He
Lizhu Zhang
Yanfei Jing
Xiaohong Rui
Shiliang Zhang
author_facet Jun Liu
Hui Ding
Mingjie Zhao
Fan Tu
Tian He
Lizhu Zhang
Yanfei Jing
Xiaohong Rui
Shiliang Zhang
author_sort Jun Liu
collection DOAJ
description 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.
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spelling doaj.art-e398b11bb14e40d3a2bdc775bb4fe3882022-12-22T03:28:29ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-06-011310.3389/fmicb.2022.901979901979Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced SepsisJun Liu0Hui Ding1Mingjie Zhao2Fan Tu3Tian He4Lizhu Zhang5Yanfei Jing6Xiaohong Rui7Shiliang Zhang8Department of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of General Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaNanxin Pharm, Nanjing, ChinaDepartment of Function, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaDepartment of Laboratory Medicine, Wuxi Fifth People’s Hospital Affiliated to Nantong University, Wuxi, ChinaSepsis 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.https://www.frontiersin.org/articles/10.3389/fmicb.2022.901979/fullsepsisKlebsiella pneumoniaeγ3 peptidetargeted therapyred blood cell membrane
spellingShingle Jun Liu
Hui Ding
Mingjie Zhao
Fan Tu
Tian He
Lizhu Zhang
Yanfei Jing
Xiaohong Rui
Shiliang Zhang
Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
Frontiers in Microbiology
sepsis
Klebsiella pneumoniae
γ3 peptide
targeted therapy
red blood cell membrane
title Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
title_full Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
title_fullStr Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
title_full_unstemmed Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
title_short Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
title_sort functionalized erythrocyte membrane coated nanoparticles for the treatment of klebsiella pneumoniae induced sepsis
topic sepsis
Klebsiella pneumoniae
γ3 peptide
targeted therapy
red blood cell membrane
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.901979/full
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