Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

Abstract

BackgroundThe special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection.MethodsCellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration.ResultsInternalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period.ConclusionOur data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0222-4) contains supplementary material, which is available to authorized users.

Gold nanoparticles improve metabolic profile of mice fed a high-fat diet

“…Increased oxidative stress has been suggested to be the major cause of organ toxicity [ 40 ]. Increased ROS production appeared in macrophages treated with high concentration of AuNP in line with reduced cell viability, consistent with the literature [ 41 , 42 ]; however such changes diminished with the co-culture with adipocytes suggesting unknown antioxidative mechanism due to the interaction between these two cell types. Similarly, AuNP treatment of adipocytes cultured alone did not change their differentiation rate into mature adipocytes, nor metabolic markers.…”

In Vivo Comparison of the Biodistribution and long-term Fate of Colloids – Gold Nanoprisms and Nanorods – With Minimum Surface Modification

“…Both the visualization of the tissues by H&E staining (Figure 2a) and the weight monitoring (Figure 2b) showed neither significant changes in terms of weight, nor drastic microscopic alterations in the organ morphology compared with the control groups. However, a considerable microvesicular steatosis was observed in the liver at the groups with the maximum gold signal, which was also observed in a previous study [30]. Moreover, these microscopic alterations were correlated with a significant splenomegaly during the first 24 h post injection.…”

“…The lack of toxicity of the nanoparticles was studied in vitro in our previous research (Alfranca, Artiga et al, 2016) as well as collaborators [30]. During the in vivo studies described herein, the low toxicity was further confirmed by monitoring the changes in the weight of the mice, by hematoxylin-eosin staining (H&E) of the tissues and also by monitoring the changes in weight of the organs collected.…”

The impact of nanoparticle-driven lysosomal alkalinization on cellular functionality

“…Despite a difference in the degree of autophagy, SiO 2 NPs still induced significant levels of autophagy, but this has no effect whatsoever on the cytoskeletal network. Previous studies have reported clear effects of various NPs including iron oxide, silver and gold on cell size and cytoskeletal network, predominantly affecting actin fibers [ 6 , 44 – 47 ], while this effect was not observed for silica NPs [ 48 ]. Silica NPs have however been observed to affect tubulin fibers [ 49 ].…”