Using gold nanorods core/silver shell nanostructures as model material to probe biodistribution and toxic effects of silver nanoparticles in mice

Abstract

The aim of this work was to probe the biodistribution and toxic effects of silver nanoparticles (NPs) with powerful anti-bacterial and anti-virus activities. For this purpose, novel silver NPs with gold nanorod (NR) core and silver shell (Au@Ag NRs) were developed and employed as a model material. The inner gold core provided an excellent internal reference for tracking the NRs in vivo. After subcutaneous injection of Au@Ag NRs, silver and gold contents in the subcutis and organs were examined by inductively coupled plasma mass spectrometry at different time points within 28 days. Histological analysis, physiological function and complement faction 3 (C3) and 5a (C5a) measurement were performed over time to reveal the toxic effect of Au@Ag NRs in vivo. Experimental results showed that majority of the Au@Ag NRs remained in the injection site except for a small amount migrating into the lymph nodes. The silver shell was dissolved in the subcutaneous tissue and released silver ions rapidly, which resulted in detectable silver accumulation in most of the organs. The accumulated silver ions in the kidney not only interacted with the kidney cells membrane but also induced a rapid increase of complement fraction C3 followed by a significant consumption and C3a and C5a production significantly in the serum, which resulted in kidney oxidative damage and eventually led to the morphological changes and filtration function impairment of the glomerulus. The released silver ions also caused oxidative injury of subcutaneous tissue in the injection site.

Main trends of immune effects triggered by nanomedicines in preclinical studies

“…The cascade of different reactions generates three major effects: 1) proinflammatory process with the release of anaphylatoxins, 2) opsonization of pathogen, which is subsequently eliminated by the phagocytic cells and 3) membrane attack complex leading directly to lysis of the targeted pathogen cell. All three pathways classical, lectin and alternative pathway, can be activated in contact with NPs, [30][31][32][33] leading to the inflammatory process 34 accumulation in the liver and spleen macrophages 35 or hypersensitivity reactions ( Figure 4). Furthermore, particle recognition by the reactive intravascular macrophages can additionally enhance the release of anaphylatoxin and the proinflammatory reactions as recently confirmed by Wibroe et al 36 The resulting CARPA is a frequent side effect of IV administered liposomal and micelle drugs already on the market or in the development stage ( Figure 3).…”

“…• Complement detection in the plasma (C3, C3a, C5a, SC5b-9, hemolytic assays) 31,34,42 • Hypersensitivity reactions 38,39,114 Pigs, mice, rats, patients, human blood Not covered by the existing guidelines for medicinal products Covered by ISO 10993-4 for medical devices Adaptive immune response…”

Comparison of 20 nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

“…Meng et al 72 used gold-core Agshell nanorods to probe the biodistribution and toxic effect of silver NPs in mice. Using gold as a particle tracer made it possible to compare the particle distribution versus the Ag distribution, and they found limited distribution of particles relative to the much wider distribution of dissolved Ag.…”

CEffect of Silver Nanoparticles Versus Titanium Dioxide Nanoparticles on the Lung of Adult Male Albino Rats: A histological and immunohistochemical study

“…Another supposed mechanism is, Ag-Nps entering into the peripheral tissue can dissolve Ag ions, that resulting local high concentration of Ag ions that induce the oxidative damage on the membrane of cells, which induced inflammatory infiltration around the vessels [64,65] .…”