The impact of cationic solid lipid nanoparticles on human neutrophil activation and formation of neutrophil extracellular traps (NETs).
Cationic solid lipid nanoparticles (cSLNs) are extensively employed as the nanocarriers for drug/gene targeting to tumors and the brain. Investigation into the possible immune response of cSLNs is still lacking. The aim of this study was to evaluate the impact of cSLNs upon the activation of human polymorphonuclear neutrophil cells (PMNs). The cytotoxicity, pro-inflammatory mediators, Ca(2+) mobilization, mitogen-activated protein kinases (MAPKs), and neutrophil extracellular traps (NETs) as the indicators of PMN stimulation were examined in this work. The cSLNs presented a diameter of 195 nm with a zeta potential of 44 mV. The cSLNs could interact with the cell membrane to produce a direct membrane lysis and the subsequent cytotoxicity according to lactate dehydrogenase (LDH) elevation. The interaction of cSLNs with the membrane also triggered a Ca(2+) influx, followed by the induction of oxidative stress and degranulation. The cationic nanoparticles elevated the levels of superoxide anion and elastase by 24- and 9-fold, respectively. The PMN activation by cSLNs promoted the phosphorylation of p38 and Jun-N-terminal kinases (JNK) but not extracellular signal-regulated kinases (ERK). The imaging of scanning electron microscopy (SEM) and immunofluorescence demonstrated the production of NETs by cSLNs. This phenomenon was not significant for the neutral SLNs (nSLNs), although histones in NETs also increased after treatment of nSLNs. Our results suggest an important role of cSLNs in governing the activation of human neutrophils.
Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Tsong-Long
TL
Hwang
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ibrahim A
IA
Aljuffali
School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan, Taiwan.
Chi-Feng
CF
Hung
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Chun-Han
CH
Chen
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
Jia-You
JY
Fang
D000328:Adult; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000008:administration & dosage*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D065206:Extracellular Traps / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010196:Pancreatic Elastase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002412:Cations; D008055:Lipids; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010196:Pancreatic Elastase; D002118:Calcium
Cationic solid lipid nanoparticles; Degranulation; Neutrophil; Neutrophil extracellular trap; Respiratory burst