In vivo evaluation of safety, biodistribution and pharmacokinetics of laser-synthesized gold nanoparticles

Abstract

Capable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.

Numerical Investigation of Ultrashort Laser-Ablative Synthesis of Metal Nanoparticles in Liquids Using the Atomistic-Continuum Model

“…The change of bimodal NP size distribution due to adding a solvent into the water media can be explained in terms of diffusion process, which is Additionally, the experimental measurements show that one can achieve the generation of a single distribution only. This is possible either by means of changing the irradiation parameters [14,30] or by means of adding different solvents [12,20,28,29]. While the effect of the irradiation parameters were accounted for in both theories of two distributions generation suggested above due to the same MD-TTM approach used [39], both Molecular Dynamics models used for water [43,50] did not include any chemistry since the possibility for the electron density changes, which can lead to the establishment of new type of bonding (chemical reactions, dissociation), was not considered explicitly due to its extremely high computational cost.…”

“…In the absence of ligands, the colloidal NPs are stable [16] and have bare (ligand-free) surface, which opens up prospects for a variety of applications in energy [21], catalysis [22] and healthcare [23,24]. As an example, we recently showed that bare Au-based NPs can provide one order of magnitude better electrocatalytic activity toward glucose oxidation compared to all chemically synthesized counterparts [25], prominent response SERS-based bioidentification tasks [26,27], as well as a much-reduced toxicity in biomedical applications [28,29].…”

The Effect of Stabilisation Agents on the Immunomodulatory Properties of Gold Nanoparticles Obtained by Ultrasonic Spray Pyrolysis

“…GNPs coupled with various molecules have been investigated extensively as a multifunctional platform for cellular imaging [4], biosensing [5] and targeted drug delivery in tumour immunotherapy and photothermal therapy [6][7][8]. Due to the chemically inert nature of Au, GNPs are expected to be biocompatible, as we demonstrated previously [9], along with several other groups [10][11][12][13]. In contrast, some publications addressed their adverse effects [14][15][16][17], which has raised concern about their impact on human health.…”

Noble Metals and Soft Bio-Inspired Nanoparticles in Retinal Diseases Treatment: A Perspective

“…Regarding the biodistribution, a recent work demonstrated a rapid elimination of colloidal AuNPs from blood circulation in a rats model, and liver and spleen accumulation without inducing adverse effects or inflammation [59]. Au comprised in passion fruit-like nanoarchitectures (NAs) were studied in murine models demonstrating the excretion by renal and biliary pathways without nephrotoxicity up to 150 mg kg −1 [60].…”