Comparisons of the biodistribution and toxicological examinations after repeated intravenous administration of silver and gold nanoparticles in mice

Abstract

Nanoparticles (NPs) size, surface functionalization, and concentration were claimed to contribute to distribution and toxicity outcomes of NPs in vivo. However, intrinsic chemical compositions of NPs caused inconsistent biodistribution and toxic profiles which attracted little attention. In this study, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were used to determine the biodistribution, toxickinetic, and genotoxicity variances in murine animals. The results demonstrated AgNPs and AuNPs were primarily deposited in the mononuclear phagocyte system (MPS) such as the liver and spleen. In particular, AuNPs seemed to be prominently stored in the liver, whereas AgNPs preferentially accumulated in more organs such as the heart, lung, kidney, etc. Also, the circulation in the blood and fecal excretions showed higher AgNPs contents in comparison with the AuNPs. Measurements of the mouse body and organ mass, hematology and biochemistry evaluation, and histopathological examinations indicated slight toxic difference between the AgNPs and AuNPs over a period of two months. RT-qPCR data revealed that AgNPs induced greater changes in gene expression with relevance to oxidative stress, apoptosis, and ion transport. Our observations proved that the NPs chemical composition played a critical role in their in vivo biodistribution and toxicity.Inorganic nanoparticles (NPs) have attracted increasing attention and are used in many fields, such as biomedicine, various industries, and electronics due to their excellent physicochemical properties 1, 2 . Currently, silver nanoparticles (AgNPs) are one of the most widely used NPs in commercial products (e.g. wound dressings, contraceptive devices, and packaging materials) because of their strong antimicrobial and anti-inflammatory properties 2, 3 . Gold nanoparticles (AuNPs) offer a wide range of applications including cosmetics, chemical sensing, drug carriers, bioimaging, and gene therapy 4,5 . The extended use of these inorganic NPs can lead to frequent human exposure via various routes (e.g. ingestion, inhalation and dermal contact) during manufacture, use and disposal. Moreover, compared with their bulk counterparts, AgNPs and AuNPs hold greater surface area to volume ratio, higher particle reactivity, and can undergo surface modifications which could result in greater side effects once these are absorbed into the body 6 . It is therefore imperative to understand the potential biological responses to AgNPs and AuNPs in vivo.Indeed, previous in vitro studies demonstrated that inorganic NPs can induce the production of reactive oxygen species (ROS), DNA damage, and apoptosis 7-10 . These observations resulted in a number of in vivo rodent studies that were focused on the toxicity or biokinetics of inorganic NPs following various administration routes 6, . Table S1 summarized the biodistribution and/or toxicity profile of various types of AgNPs and AuNPs in rodents following oral, instillation, inhalation, and intraperitoneal exposures. Prolonged inhalational exposure ...

Genotoxicity of Silver Nanoparticles

“…Biodistribution analysis is essential to understand the behavior of NPs in organisms and to select the tissue to be analyzed for genotoxicity. In general, AgNPs accumulate primarily in the mononuclear phagocyte system (MPS) such as liver and spleen after both oral [108] and intravenous administration [42]. AgNPs accumulation in liver is due to thiol-silver complexes, as silver tends to bind sulfur [108].…”

Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure

“…In a recent study, comparing the biodistribution and toxicological examinations after repeated i.v. administration of AgNPs and AuNPs in mice showed a higher deposition of AgNPs in the heart, the lung, and the kidney than that of AuNPs [175]. Moreover, the AgNPs induced adverse effects in a dose-dependent manner (the concentrations tested were 4, 10, 20, and 40 mg/kg) [175].…”

“…Cases of argyria (a condition characterized by an irreversible gray or bluish gray pigmentation of the skin), irreversible neurologic toxicity, and death have been reported upon the long-term ingestion of colloidal silver [174]. The liver appears to be a major accumulation site of circulatory AgNPs [175]. In fact, PVP-AgNPs (20-30 nm) have been shown to increase oxidative stress, enhance autophagy, and deplete insulin signaling pathways following oral exposure for 90 days in the liver of male rats [173].…”

Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Nondissected Murine Lungs

“…To achieve this goal, several common ex vivo assays, including transmission electron microscopy (TEM), 2D stereological methods, flow cytometry, and ICP-MS were applied to examine and/or quantify NP localization and distribution at cellular resolution, but the information on 3D tissue architecture was totally destroyed. [20][21][22] Currently, no available technique is able to both visualize the spatial distribution of NPs and quantify their accumulated dose in entire organs (e.g. lungs) with cellular resolution.…”