Issue 21, 2013

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

Abstract

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.

Graphical abstract: Structure–activity relationships for biodistribution, pharmacokinetics, and excretion of atomically precise nanoclusters in a murine model

Supplementary files

Article information

Article type
Paper
Submitted
17 Jun 2013
Accepted
31 Aug 2013
First published
03 Sep 2013

Nanoscale, 2013,5, 10525-10533

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

O. A. Wong, R. J. Hansen, T. W. Ni, C. L. Heinecke, W. S. Compel, D. L. Gustafson and C. J. Ackerson, Nanoscale, 2013, 5, 10525 DOI: 10.1039/C3NR03121G

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