The biodistribution and immuno-responses of differently shaped non-modified gold particles in zebrafish embryos

Abstract

Important questions raised in (nano)ecotoxicology are whether biodistribution of nanoparticles (NPs) is affected by particle shape and to what extent local adverse responses are subsequently initiated. For nanomedicine, these same questions become important when the labeled NPs lose the labeling. In this study, we investigated the biodistribution patterns of gold nanoparticles (AuNPs) as well as immune-related local and systemic sublethal markers of exposure and behavioral assessment. Hatched zebrafish embryos were exposed to four differently shaped non-coated AuNPs with comparable sizes: nanospheres, nanorods, nano-urchins, and nanobipyramids. Shape-dependent trafficking of the particles resulted in a different distribution of the particles over the target organs. The differences across the distribution patterns indicate that the particles behave slightly different, although they eventually reach the same target organsyet in different ratios. Mainly local induction of the immune system was observed, whereas systemic immune responses were not clearly visible. Macrophages were found to take AuNPs from the body fluid, be transferred into the veins and transported to digestive organs for clearance. No significant behavioral toxicological responses in zebrafish embryos were observed after exposure. The trafficking of the particles in the macrophages indicates that the particles are removed via the mononuclear phagocytic system. The different ratios in which the particles are distributed over the target organs indicate that the shape influences their behavior and eventually possibly the toxicity of the particles. The observed shape-dependent biodistribution patterns might be beneficial for shape-specific targeting in nanomedicine and stress the importance of incorporating shape-features in nanosafety assessment.

Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

“…According to the Guide for the Care and Use of Laboratory Animals, initial in vivo studies for novel nanoparticle formulations are tested in the lowest order vertebrate animal model, allowing for high throughput, minimal cost, and clinical relevance. Recognizing these criteria, an increasing body of evidence points to embryonic and adult zebrafish as an ideal model for initial toxicity and clearance studies [36,120,141,142,143]. The zebrafish’s translucent body allows for in vivo imaging techniques not possible in mammalian models, such as fluorescence microscopy [36,120,142,144,145] and two photon multifocal microscopy [142].…”

“…Recognizing these criteria, an increasing body of evidence points to embryonic and adult zebrafish as an ideal model for initial toxicity and clearance studies [36,120,141,142,143]. The zebrafish’s translucent body allows for in vivo imaging techniques not possible in mammalian models, such as fluorescence microscopy [36,120,142,144,145] and two photon multifocal microscopy [142]. The similarity in nanoparticle clearance mechanisms is thought to result from a conserved innate and adaptive immune system between adult zebrafish and mammals [146,147].…”

VASCULAR RESPONSEs TO THE SUBCUTANEOUS INJECTION OF GOLD NANOPARTICLES

“…Despite numerous studies on the possibility of using gold nanoparticles in the development of new antibiotics, their use is not yet possible due to the presence of side effects and the lack of data on their generalized effect on not only humans, but also experimental animals [5,13,2,17]. The limited use of nanoparticles is due to the fact that gold compounds are toxic, accumulate in the kidneys, liver, spleen and hypothalamus, which can lead to organic diseases and dermatitis, stomatitis and thrombocytopenia [16,11].…”

The generation of stabilized supramolecular nanorods from star-shaped polyglutamates

“…11 Van Pomeren et al also established that the shape of gold nanoparticles determined biodistribution in zebrafish embryos. 12 Aqueous shaping of soft-matter nanoparticles and polyelectrolytes, in particular, remains a complicated issue due to multiple repulsive interactions, though non-spherical polyelectrolyte particles can open new avenues in drug delivery studies.…”