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

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• 作者：Martin Sch盲ffler ; Fern ; a Sousa ; Alex ; er Wenk ; Leopoldo Sitia ; Stephanie Hirn ; Carsten Schleh ; Nadine Haberl ; Martina Violatto ; Mara Canovi ; Patrizia Andreozzi ; Mario Salmona ; Paolo Bigini ; Wolfgang G. Kreyling ; Silke Krol
• 关键词：Biodistribution ; Biokinetics ; Protein gold nanoparticle conjugate ; Blood&ndash ; brain barrier ; Albumin ; Apolipoprotein E
• 刊名：Biomaterials
• 出版年：March, 2014
• 年：2014
• 卷：35
• 期：10
• 页码：3455-3466
• 全文大小：2790 K

文摘

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聽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聽nm double fluorescently-labeled alb-AuNP-conjugates. Protein conjugation massively reduced liver retention (alb-AuNP: 52%, apoE-AuNP: 72%, cit-AuNP: >95%, at 19聽h and 48聽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聽h. Alb-AuNP show significantly increased fractions in lungs (factors: 60 (30聽min); 111 (19聽h); 235 (48聽h) and brain (factors: 70 (30聽min); 90 (19聽h); >200 (48聽h) compared to cit-AuNP (control) - or even to apoE-AuNP. The influence of protein conjugation on the biodistribution disappears for 80聽nm AuNP comparing to control. Histologically, the 15聽nm alb-AuNP are mainly located in the endothelium of brain, lungs, liver and kidneys after 30聽min, while at 19聽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.