Long-Term Biodistribution and Safety Profile of Laser-Generated Gold Nanoparticles Following High-Dose Administration in Mice

Abstract

Gold nanoparticles (AuNPs) have emerged as versatile agents for a wide range of biomedical applications, including imaging, diagnostics, and therapy. While their use in modalities such as CT imaging and radiotherapy is particularly promising, these applications require high systemic doses (≥500 mg Au/kg), necessitating thorough evaluation of long-term biodistribution and safety profiles. Here, we present a comprehensive one-year assessment of Polyethylene glycol (PEG) -coated laser-synthesized AuNPs (mean core diameter ∼8 nm). After intravenous administration at a high dose, biodistribution was evaluated in healthy mice (n = 8; 874 ± 56 mg Au/kg) using a serial CT imaging, with terminal ICP-AES validation, blood biochemistry, and histology performed in 5 of these animals. AuNPs exhibited prolonged blood circulation (half-life 21 ± 3 h) and accumulated predominantly in reticuloendothelial organs: 42.2 ± 3.6%ID/cm3 in the liver and 40.2 ± 3.3%ID/cm3 in the spleen, with one-year retention of 77.5% and 83.1%, respectively. Despite substantial hepatic and splenic retention, no histopathological changes were detected in any major organs, including kidney and liver. Serum biochemical markers of liver, kidney, and pancreatic function revealed no statistically significant differences between the treated and control groups. Only a slight elevation in aspartate aminotransferase (AST) was observed in two treated animals (184.1 and 187.8 U/L vs 118.3 ± 18.4 U/L in the control group), while all other liver function markers (ALT, alkaline phosphatase, bilirubin) remained unaltered. Additionally, tumor uptake was evaluated in two separate cohorts of mice bearing subcutaneous tumor models, mammary adenocarcinoma Ca755 (n = 3, 809 ± 28 mg Au/kg) and melanoma B16F10 (n = 3, 814 ± 45 mg Au/kg). AuNPs accumulated in tumor tissue, reaching 9.4 ± 1.9%ID/cm3 for Ca755 and 5.3 ± 1.1%ID/cm3 for B16F10. Overall, these results provide insight into the safety profile and tumor uptake of laser-synthesized AuNPs, supporting their potential as a platform for novel radiosensitizers and contrast agents.