International Journal of Nanomedicine (May 2024)

Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys

  • Jakic K,
  • Selc M,
  • Razga F,
  • Nemethova V,
  • Mazancova P,
  • Havel F,
  • Sramek M,
  • Zarska M,
  • Proska J,
  • Masanova V,
  • Uhnakova I,
  • Makovicky P,
  • Novotova M,
  • Vykoukal V,
  • Babelova A

Journal volume & issue
Vol. Volume 19
pp. 4103 – 4120

Abstract

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Kristina Jakic,1 Michal Selc,1,2 Filip Razga,3 Veronika Nemethova,3 Petra Mazancova,3 Filip Havel,4,5 Michal Sramek,5 Monika Zarska,5 Jan Proska,4 Vlasta Masanova,6 Iveta Uhnakova,6 Peter Makovicky,7 Marta Novotova,8 Vit Vykoukal,9 Andrea Babelova1,2 1Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 2Centre for Advanced Material Application, Slovak Academy of Sciences, Bratislava, Slovakia; 3Selecta Biotech SE, Bratislava, Slovakia; 4Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 5Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic; 6Department of Metallomics, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia; 7Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 8Department of Cellular Cardiology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 9Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech RepublicCorrespondence: Andrea Babelova, Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia, Tel +421-2-32295-189, Fax +421-2-5477-4284, Email [email protected]: Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms.Methods: We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days.Results: The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues.Conclusion: Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications. Keywords: AuNPs, in vivo, long-term accumulation, biodistribution, inflammation, fibrosis

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