Blood protein coating of gold nanoparticles as potential tool for organ targeting.
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; (198)Au 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.
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
Martin
M
Schäffler
IRCCS Foundation Institute for Neurology "Carlo Besta", IFOM-IEO-Campus, Milan, Italy.
Fernanda
F
Sousa
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
Alexander
A
Wenk
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Leopoldo
L
Sitia
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
Stephanie
S
Hirn
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
Carsten
C
Schleh
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
Nadine
N
Haberl
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Martina
M
Violatto
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Mara
M
Canovi
IRCCS Foundation Institute for Neurology "Carlo Besta", IFOM-IEO-Campus, Milan, Italy.
Patrizia
P
Andreozzi
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Mario
M
Salmona
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Paolo
P
Bigini
Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Munich, Germany. Electronic address: kreyling@helmholtz-muenchen.de.
Wolfgang G
WG
Kreyling
IRCCS Foundation Institute for Neurology "Carlo Besta", IFOM-IEO-Campus, Milan, Italy. Electronic address: silke.krol@ifom.eu.
Silke
S
Krol
D001798:Blood Proteins / Q000737:chemistry*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles; D014018:Tissue Distribution
D001798:Blood Proteins; D005456:Fluorescent Dyes; D006046:Gold
Albumin; Apolipoprotein E; Biodistribution; Biokinetics; Blood–brain barrier; Protein gold nanoparticle conjugate