In vivo integrity of polymer-coated gold nanoparticles.

Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

[1]  Brahim Lounis,et al.  Cathepsin L digestion of nanobioconjugates upon endocytosis. , 2009, ACS nano.

[2]  Luis M Liz-Marzán,et al.  Physicochemical properties of protein-coated gold nanoparticles in biological fluids and cells before and after proteolytic digestion. , 2013, Angewandte Chemie.

[3]  Manuela Semmler-Behnke,et al.  Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. , 2010, Biomaterials.

[4]  T. R. Pisanic,et al.  Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality. , 2010, Small.

[5]  Manuela Semmler-Behnke,et al.  Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  Teófilo Rojo,et al.  The challenge to relate the physicochemical properties of colloidal nanoparticles to their cytotoxicity. , 2013, Accounts of chemical research.

[7]  Lutz Trahms,et al.  Efficient drug-delivery using magnetic nanoparticles--biodistribution and therapeutic effects in tumour bearing rabbits. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[8]  Sabine Neuss,et al.  Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. , 2009, Small.

[9]  V. Rasche,et al.  Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. , 2010, Biomaterials.

[10]  Fengjuan Wang,et al.  The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[11]  Matthias Epple,et al.  TOXICITY OF SILVER NANOPARTICLES INCREASES DURING STORAGE BECAUSE OF SLOW DISSOLUTION UNDER RELEASE OF SILVER IONS , 2010 .

[12]  Manuela Semmler-Behnke,et al.  Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration , 2011, Nanotoxicology.

[13]  R. Niessner,et al.  Multifunctional nanoparticles for dual imaging. , 2011, Analytical chemistry.

[14]  Wolfgang J. Parak,et al.  The Toxicity of Silver Nanoparticles Depends on Their Uptake by Cells and Thus on Their Surface Chemistry , 2013 .

[15]  W. Kreyling,et al.  Interspecies Comparison of Phagolysosomal pH in Alveolar Macrophages , 1991 .

[16]  Thomas Pons,et al.  Fluorine-18-labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales. , 2008, Bioconjugate chemistry.

[17]  Duxin Sun,et al.  Intracellular dissociation of a polymer coating from nanoparticles , 2012, Nano Research.

[18]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[19]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[20]  F. Gendron,et al.  Long term in vivo biotransformation of iron oxide nanoparticles. , 2011, Biomaterials.

[21]  K. Böse,et al.  A Correlative Analysis of Gold Nanoparticles Internalized by A549 Cells , 2014 .

[22]  Manuela Semmler-Behnke,et al.  Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size. , 2014, ACS nano.

[23]  Manuela Semmler-Behnke,et al.  Biodistribution of 1.4- and 18-nm gold particles in rats. , 2008, Small.