Quantitative Biokinetics and Systemic Translocation of Various Gold Nanostructures Are Highly Dependent on Their Size and Shape

Abstract

Gold nanostructures with promising applications in biomedical field have attracted great attention. However, some fundamental questions other than the development of novel applications should be elucidated before they can actually serve as biomedicines in the clinic. Bio-safety is one of the most important issues. Since numerous modifications (e.g., surface coating and composites) have been designed on gold nanoparticles (GNPs) to extend their application, there would be hundreds of GNPs synthesized in the lab although the prototypes of GNPs (i.e., cluster, shell, rod, sphere, cage, and star) are rather limited. Thus, in the present work we aim to conduct our experiments only on the most basic types of GNPs--including gold nanocluster (GNC), gold nanorod (GNR) and gold nanosphere (GNS), to investigate their biodistribution and toxicities in vivo, in the hope of revealing some basic rules which could be further extended to other complicated situations. Bovine serum albumin (BSA) was coated at the surface to increase their plasma stability and of the same BSA coating would help to compare the fate and behaviors of various GNPs in vivo. After intravenous administration of different GNPs with an equal content of gold element at 0.5 mg/kg in mice, samples were harvested at a series of time points. Biodistribution was compared among different GNPs and the process of accumulation-retention-clearance of each kind of GNP was also observed through quantification analysis by inductively coupled plasma-mass spectrometry (ICP-MS). The results showed, with the same BSA coating at the surface and similar negative charge, size rather than shape was dominating the in vivo fate of GNPs. Even between GNC and hydrolyzed GNC with their size at 7.1 and 3.2 nm, huge difference in the kidney accumulation was observed. Totally, GNR and GNS in relative large size preferred to accumulate in liver and spleen whereas GNC in relative small size tended to accumulate in liver and kidney. GNPs resided in liver were hardly cleared out of body till 28 d whereas their accumulation in kidney was almost entirely eliminated with prolonged time, although not as rapid as reported in previous work. In vivo toxicities evaluated by pathology observation and blood biochemical analysis also revealed slight liver and kidney damage, basically associated with the biodistribution pattern of GNPs.

Mapping the Glyco-Gold Nanoparticles of Different Shapes Toxicity, Biodistribution and Sequestration in Adult Zebrafish

“…Since the AuNPs were non-toxic, it is worth to study their biodistribution and sequestration to target the specific organ using different shapes 31–33 and carbohydrate receptors. To this end, PEGylated and mannose-AuNPs (5 µg/g) of different shapes were intraperitoneally injected into zebrafish (Fig.…”

Rational Design of Biomolecular Templates for Synthesizing Multifunctional Noble Metal Nanoclusters toward Personalized Theranostic Applications

“…The nucleus‐targeting Au NCs exhibited high gene transfection efficiencies in both in vitro and in vivo studies, thus demonstrating the superior gene‐delivery property of biomolecule‐capped Au NCs. Apart for nucleus‐targeting TAT peptide, other biorecognition elements such as folic acid,[18b] epidermal growth factor receptor antibody and cyclic RGD, can be incorporated into the NC for active targeting (Figure B). The combination of active targeting and passive accumulation (EPR effect) can greatly enhance the tissue targeting specificity of metal NCs.…”

“…Apart from delivery, NC biodistribution is another concern that must be considered. Metal NCs have to be sufficiently stable in the blood plasma as they are being trafficked to their specific destinations to fulfil their respective functions . At the same time, efficient renal clearance is required to minimize potential side‐effects arising from prolonged NC accumulation (Figure C).…”

Nanogold – Biological effects and occupational exposure levels

“…[23] również opisali różnice w rozmieszczeniu nanoobiektów złota o różnych kształtach. Badali oni występowanie nanozłota w kształcie: klastrów (mniejsze cząstki), prętów i sfer (większe cząst-ki) u myszy, którym wstrzykiwali dożylnie pojedynczą dawkę (0,5 mg/kg mc.).…”