Monday, July 20, 2009

Dotting the Quantum I's - Engineered nanoparticle toxicity

BrooklynDodger(s): Quantum Dots are engineered nanoparticles, which might be really commentexotic compared to the run of the mill carcinogenic nano particles like diesel particulate matter, carbon black and titanium dioxide. Too bad this investigation didn't explore relative potency between QD's - unlikely to ever undergo an inhalation bioassay, much less present a study in people - with the already known species.


Toxicology and Applied Pharmacology
Volume 238, Issue 2, 15 July 2009, Pages 160-169


Nanoparticles up-regulate tumor necrosis factor-α and CXCL8 via reactive oxygen species and mitogen-activated protein kinase activation

Hye-Mi Leea, b, Dong-Min Shina, b, Hwan-Moon Songc, Jae-Min Yuka, b, Zee-Won Leed, Sang-Hee Leee, Song Mei Hwangf, Jin-Man Kimf, Chang-Soo Leec, Corresponding Author Contact Information, E-mail The Corresponding Author and Eun-Kyeong Joa, b, g, Corresponding Author Contact Information, E-mail The Corresponding Author

aDepartment of Microbiology, College of Medicine, Daejeon 301-747, South Korea

bInfection Signaling Network Research Center, College of Medicine, Daejeon 301-747, South Korea

cDepartment of Chemical Engineering, College of Engineering, Chungnam National University, Daejeon 305-764, South Korea

dGlycomics Team, Korea Basic Science Institute, Daejeon 305-333, South Korea

eMolecular Genomics Laboratory, Department of Biological Science, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, South Korea

fDepartment of Pathology, College of Medicine, Daejeon 301-747, South Korea

gResearch Institute for Medical Sciences, College of Medicine, Daejeon 301-747, South Korea

Abstract

Evaluating the toxicity of nanoparticles is an integral aspect of basic and applied sciences, because imaging applications using traditional organic fluorophores are limited by properties such as photobleaching, spectral overlaps, and operational difficulties. This study investigated the toxicity of nanoparticles and their biological mechanisms. We found that nanoparticles, quantum dots (QDs), considerably activated the production of tumor necrosis factor (TNF)-α and CXC-chemokine ligand (CXCL) 8 through reactive oxygen species (ROS)- and mitogen-activated protein kinases (MAPKs)-dependent mechanisms in human primary monocytes. Nanoparticles elicited a robust activation of intracellular ROS, phosphorylation of p47phox, and nicotinamide adenine dinucleotide phosphate oxidase activities. Blockade of ROS generation with antioxidants significantly abrogated the QD-mediated TNF-α and CXCL8 expression in monocytes. The induced ROS generation subsequently led to the activation of MAPKs, which were crucial for mRNA and protein expression of TNF-α and CXCL8. Furthermore, confocal and electron microscopy analyses showed that internalized QDs were trapped in cytoplasmic vesicles and compartmentalized inside lysosomes. Finally, several repeated intravenous injections of QDs caused an increase in neutrophil infiltration in the lung tissues in vivo. These results provide novel insights into the QD-mediated chemokine induction and inflammatory toxic responses in vitro and in vivo.

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