Biodistribution of polyacrylic acid-coated iron oxide nanoparticles is associated with proinflammatory activation and liver toxicity.
Iron oxide nanoparticles (IONs) have physical and chemical properties that render them useful for several new biomedical applications. Still, so far, in vivo safety studies of IONs with coatings of biomedical interest are still scarce. The aim of this study, therefore, was to clarify the acute biological effects of polyacrylic acid (PAA)-coated IONs, by determining their biodistribution and their potential proinflammatory and toxic effects in CD-1 mice. The biodistribution of PAA-coated IONs in several organs (liver, spleen, kidneys, brain, heart, testes and lungs), the plasma cytokines, chemokine and aminotransferases levels, white blood cell count, oxidative stress parameters, adenosine triphosphate and histologic features of liver, spleen and kidneys were evaluated 24 h after a single acute (8, 20 or 50 mg kg(-1) ) intravenous administration of PAA-coated IONs in magnetite form. The obtained results showed that these IONs accumulate mainly in the liver and spleen and, to a lesser extent, in the lungs. Although our data showed that PAA-coated IONs do not cause severe organ damage, an inflammatory process was triggered in vivo, as evidenced by as evidenced by increased neutrophils and large lymphocytes in the differential blood count. Moreover, an accumulation of iron in macrophages of the liver and spleen was observed and hepatic lipid peroxidation was elicited, showing that the IONs are able to induce oxidative stress. The effects of these nanoparticles need to be further investigated regarding the mechanisms involved and the long-term consequences of intravenous administration of PAA-coated IONs. Copyright © 2016 John Wiley & Sons, Ltd.
UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Diana
D
Couto
UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Marisa
M
Freitas
UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Vera Marisa
VM
Costa
UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Renan Campos
0000-0002-4549-3297
RC
Chisté
LAQV-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Agostinho
A
Almeida
Laboratory of Nanotechnology and Magnetism, Institute of Technological Research, IIT, University of Santiago de Compostela (USC), Spain.
M Arturo
MA
Lopez-Quintela
International Iberian Nanotechnology Laboratory, Braga, Portugal.
José
J
Rivas
International Iberian Nanotechnology Laboratory, Braga, Portugal.
Paulo
P
Freitas
UCIBIO-REQUIMTE, Laboratory of Histology and Embryology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Paula
P
Silva
UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Félix
F
Carvalho
UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Eduarda
E
Fernandes
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D010316:Particle Size; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution
D000180:Acrylic Resins; D015415:Biomarkers; D016207:Cytokines; D058185:Magnetite Nanoparticles; C006903:carbopol 940
bioaccumulation; biodistribution; inflammation; iron oxide nanoparticles; lipid peroxidation