Structure-activity relationships for biodistribution, pharmacokinetics, and excretion of atomically precise nanoclusters in a murine model

The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecule...

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Bibliographic Details
Published inNanoscale Vol. 5; no. 21; p. 10525
Main Authors Wong, O Andrea, Hansen, Ryan J, Ni, Thomas W, Heinecke, Christine L, Compel, W Scott, Gustafson, Daniel L, Ackerson, Christopher J
Format Journal Article
LanguageEnglish
Published England 07.11.2013
Subjects
Animals
Gold - chemistry
Mice
Models, Animal
Nanoparticles - chemistry
Nanoparticles - metabolism
Structure-Activity Relationship
Surface Properties
Tissue Distribution
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Summary:The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecules in a nanomaterials preparation, or if the ADME/PK properties are ensemble properties of an entire preparation. Here we characterize the ADME/PK properties of atomically precise preparations of ligand protected gold nanoclusters in a murine model system. We constructed atomistic models and tested in vivo properties for five well defined compounds, based on crystallographically resolved Au25(SR)18 and Au102(SR)44 nanoclusters with different (SR) ligand shells. To rationalize unexpected distribution and excretion properties observed for several clusters in this study and others, we defined a set of atomistic structure-activity relationships (SAR) for nanoparticles, which includes previously investigated parameters such as particle hydrodynamic diameter and net charge, and new parameters such as hydrophobic surface area and surface charge density. Overall we find that small changes in particle formulation can provoke dramatic yet potentially predictable changes in ADME/PK.
ISSN:2040-3364
2040-3372
DOI:10.1039/c3nr03121g