Blood protein coating of gold nanoparticles as potential tool for organ targeting

Martin Schäffler, Fernanda Sousa, Alexander Wenk, Leopoldo Sitia, Stephanie Hirn, Carsten Schleh, Nadine Haberl, Martina Violatto, Mara Canovi, Patrizia Andreozzi, Mario Salmona, Paolo Bigini, Wolfgang G. Kreyling, Silke Krol

Research output: Contribution to journalArticle

Abstract

Nanoparticles (NP) and nanoparticulated drug delivery promise to be the breakthrough for therapy in medicine but raise concerns in terms of nanotoxicity. We present quantitative murine biokinetics assays using polyelectrolyte-multilayer-coated gold NP (AuNP, core diameter 15 and 80 nm; 198Au radio-labeled). Those were stably conjugated either with human serum albumin (alb-AuNP) or apolipoprotein E (apoE-AuNP), prior to intravenous injection. We compare the biokinetics of protein-AuNP-conjugates with citrate-stabilized AuNP (cit-AuNP). Biokinetics was complemented with histology in organs with high AuNP content using 15 nm double fluorescently-labeled alb-AuNP-conjugates. Protein conjugation massively reduced liver retention (alb-AuNP: 52%, apoE-AuNP: 72%, cit-AuNP: >95%, at 19 h and 48 h) when compared to cit-AuNP. The protein conjugates were retained in lungs (alb-AuNP (18%) and spleen (alb-AuNP (16%), apoE-AuNP (21%) at 19 h. Alb-AuNP show significantly increased fractions in lungs (factors: 60 (30 min); 111 (19 h); 235 (48 h) and brain (factors: 70 (30 min); 90 (19 h); >200 (48 h) compared to cit-AuNP (control) - or even to apoE-AuNP. The influence of protein conjugation on the biodistribution disappears for 80 nm AuNP comparing to control. Histologically, the 15 nm alb-AuNP are mainly located in the endothelium of brain, lungs, liver and kidneys after 30 min, while at 19 h they moved deeper into the parenchyma e.g. in hippocampus. Our study clearly suggests that stable conjugation of AuNP with albumin and apoE prior to intravenous administration increases specificity and efficiency of NP in diseased target-organs thus suggesting a potential role in nanomedicine and nanopharmacology.

Original languageEnglish
Pages (from-to)3455-3466
Number of pages12
JournalBiomaterials
Volume35
Issue number10
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Albumin
  • Apolipoprotein E
  • Biodistribution
  • Biokinetics
  • Blood-brain barrier
  • Protein gold nanoparticle conjugate

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Fingerprint Dive into the research topics of 'Blood protein coating of gold nanoparticles as potential tool for organ targeting'. Together they form a unique fingerprint.

  • Cite this

    Schäffler, M., Sousa, F., Wenk, A., Sitia, L., Hirn, S., Schleh, C., Haberl, N., Violatto, M., Canovi, M., Andreozzi, P., Salmona, M., Bigini, P., Kreyling, W. G., & Krol, S. (2014). Blood protein coating of gold nanoparticles as potential tool for organ targeting. Biomaterials, 35(10), 3455-3466. https://doi.org/10.1016/j.biomaterials.2013.12.100