title: Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size.
abstract: Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of (198)Au-radio-labeled monodisperse, well-characterized, negatively charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1, 3, and 24 h, the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows that as AuNP get smaller, they are more likely to cross the air-blood barrier (ABB) depending strongly on the inverse diameter d(-1) of their gold core, i.e., their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most, while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d(-1) relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP that had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood, and excretion via urine further declined with d(-1) of AuNP core. Translocation of 5, 18, and 80 nm AuNP is virtually complete after 1 h, while 1.4 nm AuNP continue to translocate until 3 h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge.
authors.affiliation: Institute of Lung Biology and Disease and ‡Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health , 85764 Neuherberg/Munich, Germany.
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Kreyling
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirn
authors.forename: Winfried
authors.initials: W
authors.lastname: Möller
authors.forename: Carsten
authors.initials: C
authors.lastname: Schleh
authors.forename: Alexander
authors.initials: A
authors.lastname: Wenk
authors.forename: Gülnaz
authors.initials: G
authors.lastname: Celik
authors.forename: Jens
authors.initials: J
authors.lastname: Lipka
authors.forename: Martin
authors.initials: M
authors.lastname: Schäffler
authors.forename: Nadine
authors.initials: N
authors.lastname: Haberl
authors.forename: Blair D
authors.initials: BD
authors.lastname: Johnston
authors.forename: Ralph
authors.initials: R
authors.lastname: Sperling
authors.forename: Günter
authors.initials: G
authors.lastname: Schmid
authors.forename: Ulrich
authors.initials: U
authors.lastname: Simon
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Parak
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler-Behnke
mesh_terms: D015824:Blood-Air Barrier; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D053768:Metal Nanoparticles; D010316:Particle Size; D014132:Trachea
chemical_list: D006046:Gold