Proteomic profiling reveals engineered chitosan nanoparticles mediated cellular crosstalk and immunomodulation for therapeutic application in apical periodontitis  

作　　者：Hebatullah Hussein Anil Kishen 

机构地区：[1]The Kishen Lab,Dental Research Institute,University of Toronto,Toronto,ON M5G 1G6,Canada [2]Faculty of Dentistry,University of Toronto,Toronto,ON M5G 1G6,Canada [3]Faculty of Dentistry,Ain Shams University,Endodontics Department,Cairo,Egypt [4]School of Graduate Studies,University of Toronto,Toronto,ON M5G 1G6,Canada [5]Department of Dentistry,Mount Sinai Health System,Mount Sinai Hospital,Toronto,ON M5G 1X5,Canada

出　　处：《Bioactive Materials》2022年第5期77-89,共13页生物活性材料（英文）

基　　金：supported in part by a research grant from the American Association of Endodontists Foundation[#509641];the Natural Sciences and Engineering Research Council of Canada:Discovery Grant-AK[RGPIN-2020-05844];supported by a scholarship funded by the Egyptian Ministry of Higher Education.

摘　　要：Macrophages(MQ)are major constituents of chronically inflamed periapical tissues in apical periodontitis.This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles(CSnp)antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts(PdLF).Cells viability,spreading,PdLF migration,and intracellular CSnp uptake were characterized.Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm,CSnp-treated biofilm,and CSnp.Secreted inflammatory mediators were analyzed.Following bioinformatics analyses,candidate proteins were validated via targeted proteomics.CSnp maintained cells viability,increased MQ spreading,and PdLF migration(p<0.05).Transmission electron micrographs demonstrated CSnp internalization via macropinocytosis,clathrin-mediated endocytosis,and phagocytosis.Proteomic analysis revealed that CSnp-treated biofilm upregulated proteins(>1.5-folds,p<0.05)showed functional enrichment in the pathway of metal sequestration by antimicrobial proteins,while downregulated proteins showed enrichment in ferroptosis.CSnp upregulated proteins exhibiting antioxidant and immunoregulatory properties.Upregulation of SERPINB1 by CSnp(>1.5-folds,p<0.05)was validated.CSnp-treated biofilm reduced pro-inflammatory IL-1β and nitric oxide but enhanced anti-inflammatory IL-10 and TGF-β1(p<0.05).Internalized engineered bioactive CSnp reprogrammed MQ proteomic and cytokine profiles to modulate biofilm-mediated inflammation,and prompted PdLF migration,emphasizing its potential to regulate healing process in the treatment of apical periodontitis.

关 键 词：Chitosan-based nanoparticles MACROPHAGES IMMUNOMODULATION Tandem mass tags Mass spectrometry ENDODONTICS 

分 类 号：R318[医药卫生—生物医学工程] R781.341[医药卫生—基础医学]