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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Blood protein coating of gold nanoparticles as potential tool for organ targeting.
Biomaterials 35, 3455-3466 (2014)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Albumin ; Apolipoprotein E ; Biodistribution ; Biokinetics ; Blood-brain Barrier ; Protein Gold Nanoparticle Conjugate; Particle-size; Drug-delivery; Serum-albumin; Biodistribution; Receptor; Binding; Expression; Corona; Rats; Ph
ISSN (print) / ISBN
0142-9612
e-ISSN
1878-5905
Zeitschrift
Biomaterials
Quellenangaben
Band: 35,
Heft: 10,
Seiten: 3455-3466
Verlag
Elsevier
Verlagsort
Oxford
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)