Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain.
Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Joanna
J
Seiffert
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Farhana
F
Hussain
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Coen
C
Wiegman
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Feng
F
Li
Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, United Kingdom; Department of Mechanical Engineering, Faculty of Engineering Building, University of Malaya, Kuala Lumpur, Malaysia.
Leo
L
Bey
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Warren
W
Baker
Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, United Kingdom.
Alexandra
A
Porter
Department of Material Science, Chemistry and the London Centre for Nanotechnology, Imperial College, London, United Kingdom.
Mary P
MP
Ryan
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Yan
Y
Chang
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, United States of America.
Andrew
A
Gow
Nicholas School of Environment & Duke Global Health Institute, Duke University, Durham, United States of America.
Junfeng
J
Zhang
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Jie
J
Zhu
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Terry D
TD
Tetley
Airways Disease, National Heart & Lung Institute, Imperial College, London, United Kingdom.
Kian Fan
KF
Chung
D000818:Animals; D019343:Citric Acid / Q000633:toxicity*; D020099:Coated Materials, Biocompatible / Q000633:toxicity*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000009:adverse effects*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011205:Povidone / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000633:toxicity*
D020099:Coated Materials, Biocompatible; C077842:polyvinylpolypyrrolidone; D019343:Citric Acid; D012834:Silver; D011205:Povidone