The Influence of Size and Chemical Composition of Silver and Gold Nanoparticles on in vivo Toxicity with Potential Applications to Central Nervous System Diseases

Abstract

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.

Current Knowledge of Silver and Gold Nanoparticles in Laboratory Research—Application, Toxicity, Cellular Uptake

“…Due to the development of nanotechnology and the use of nanoparticles, it is necessary to study their effects on cells. Many parameters of NPs influence toxicity, including size, shape, concentration, type of coating, and incubation time [ 33 , 106 ]. It is worth noting that response to NPs also depends on the cell type.…”

“…It is worth noting that response to NPs also depends on the cell type. Hence, to increase the safety of their use, this aspect needs to be considered, especially in the context of biomedical applications [ 106 ]. Differences in physicochemical variables make the assessment of nanoparticle toxicity a relatively complex process.…”

“…The effect of an increase in the concentration of silver nanoparticles leading to apoptosis is shown in Figure 2 . AgNP toxicity is most likely associated with their surface oxidation and the release of silver ions, which cause biochemical changes, abnormalities in cell functions, and neurotoxic modifications [ 106 , 111 ]. The nanotoxicity mechanism relies on the production of ROS, including singlet oxygen, superoxide radical ions, oxide radicals, superoxide ions, hydrogen peroxide, and hydroxyl radicals.…”

“…This may be related to the mechanism of endocytosis and exocytosis across the blood–brain barrier and confirm the accumulation of silver nanoparticles in the brain. Therefore, low levels of AgNP removal from the brain may be a risk to patients treated with products containing NPs, potentially resulting in an opposite rather than expected effect during long-term use [ 94 , 106 ].…”

Pharmacokinetics, Biodistribution, and Biosafety of PEGylated Gold Nanoparticles In Vivo

“…Recent evidence of intralysosomal biodegradation of AuNPs, which over time leads to the formation of new bio-persistent nanostructures, raises concerns about the long-term effects of retained nanoparticles in the body [ 3 ]. Because the biodegradation process is very slow, it is necessary to perform a toxicological evaluation over a longer period to obtain a complex toxicological profile and a better understanding of the whole life cycle of AuNPs in the body [ 14 ]. Despite a large number of studies carried out during the past years, AuNPs toxicity remains fragmentary and even contradictory [ 15 ].…”