Biodistribution of polyacrylic acid‐coated iron oxide nanoparticles is associated with proinflammatory activation and liver toxicity

Abstract

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 À1 ) 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.

Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

“…The administration of polyacrylic acid-coated iron oxide nanoparticles is associated with a selective distribution in the liver that produces proinflammatory activation and liver toxicity in mice. A high accumulation of iron was also observed by macrophages phagocytosis in the periportal zone of the hepatic acinus of the liver and in the splenic red pulp of the spleen which demonstrates the specific uptake of this type of nanoparticles by the monocyte-macrophage system (101).…”

Review of the effects of manufactured nanoparticles on mammalian target organs

“…According to existing studies, almost all of NPs have the ability to cause excessive ROS generation in affected organs, while metal or metal oxide NPs are more likely to induce oxidative stress that is evident from the increase in lipid peroxidation levels in liver, kidneys, and spleen. This effect has not been observed in heart tissue (Almeida et al, 2016;Couto et al, 2016;Teodoro et al, 2016).…”

“…Iron oxide NPs accumulate mainly in the liver and spleen, and to a lesser extent in the lungs. They tend to accumulate in liver phagocytes and elicit hepatic lipid peroxidation, showing the ability to induce oxidative stress (Couto, Freitas, Costa, & Chiste, ). High doses of silica nanorattle intravenous administration could induce liver and heart damages, which have shown to be related with the decreased activity of superoxide dismutase (SOD) (Fu et al, ).…”

“…Special attention should be paid to the interaction between NPs and conjugates with the immune system. First of all, NPs containing metal can trigger an inflammatory process, as has been shown by the increased differential count of neutrophils and large lymphocytes in blood (Couto et al, ). When talking about immune organs, the spleen readily comes to mind being a secondary lymphoid organ.…”

Polyacrylic Acid-Coated Iron Oxide Nanoparticles Could Be a Useful Tool for Tracking Inflammatory Monocytes

“…In the case of some chronic inflammatory diseases, when taking a sample requires an invasive procedure, specific in vivo tracking of monocytes will be useful to characterize different patterns of mononuclear infiltrates. In vivo studies in 8-week-old male CD-1 mice showed that after intravenous injection, poly(acrylic acid)-coated iron oxide nanoparticles (PAC-IONs) accumulated mainly in the liver and spleen, and at a lower extent in the lungs, without causing severe organ damage [39].…”